Chance is a young, immature American bulldog owned by a young boy named Jamie who cares for him very deeply. Given his early life, he was abandoned as a puppy and sent to the pound. Fortunately, he was adopted by Jamie and given a home. He has a very loose relationship with Jamie at first, because of the memory of his previous owner abandoned him. His pet comrades are Shadow, a wise, old golden retriever and Sassy, a Himalayan cat who is constantly annoyed by Chance's antics and is usually tortured by him. During Bob and Laura Seaver's wedding, he ended up eating the wedding cake before the newlyweds could cut it, which eventually ended up working against him where it gave him indigestion and forced him to vomit up what was left of it after launching Sassy into the sandbox. Due to his immaturity, Chance has a tendency to get himself (as well as his pet comrades) in trouble. He considers Shadow an old fusspot and calls him "old timer", but still has respect for him. His fear of going to "the bad place", AKA the pound, seen in the second film leads him and the others to be left behind. The second film also implies he has a bit of a paranoid nature to him, as he vomited up a green kibble (implied to be a sedative) due to thinking the owners were going to do something bad to him and the other pets.
Chance narrates how he used to be a stray dog living his life as he saw it until one day it landed him in the dog pound. Not wanting to go into detail about his time there, he instead skips to when he was given his second chance when he was adopted by the Seaver family and now lived with them, being first seen chewing up some clothes while outside, the wedding between Bob and Laura was taking place. When Sassy comes in to confront him, it is not long before Sassy provokes Chance into chasing her, causing a ruckus in the house that draws attention from the wedding guests outside and also from Shadow, who intends to deal with Chance before Peter talks him down, before the ceremony continues.
Later, during the reception, Chance is sniffing out the chef and tries begging for food, but the chef refuses. When Chance spots a large turkey and prepares to dig into it, Shadow growls a warning, but when Chance tells him off, Shadow threatens to alert the Seavers as he barks to try and get their attention, and Chance backs off. He later decides to go after the wedding cake and ends up being caught devouring it when it came time for Bob and Laura to cut it. Later on outside, he has some fun at Sassy and Hope's expense when he uses the see-saw to catapult Sassy into the sandbox. While Hope takes a freaking out Sassy inside to tell Laura what happened, Chance gets his karmic payback for both that and eating the wedding cake earlier when he feels sick and throws it back up, to Peter and Jamie's disgust. Apparently, this occurred in little enough time that he hadn't had time to properly digest the cake, as Jamie in particular immediately recognized the contents of the resulting vomit as being their maternal grandma's wedding cake.
Later on, the pets are taken by the Seavers to stay with their family friend Kate while getting settled back home. Chance takes to liking the farm but gets scared out of his mind when he encounters a large turkey while chasing the chickens. When Kate decides to head out on a cattle drive, leaving the pets in the care of her friend Frank, this causes Chance to become uneasy, reminding him of the pound, but Shadow sees things differently, thinking the Seavers have been gone way too long and is deeply concerned. Chance believes and accepts at first that they had been abandoned, having previously experienced that as a puppy, but Shadow refuses to agree.
- “Wake up and smell the kibble. They dumped us."
"No! It isn't true!"
"They love you and they dump you."
- ―Shadow refuses to believe Chance's claims the Seavers disowned them
Refusing to believe the Seavers have abandoned them, Shadow decides that if Peter can't come to him, he's going to Peter. He's going home. Sassy decides to come with him, but Chance refuses, staying on the farm until the turkey reappears, frightening Chance into joining Shadow and Sassy as they prepare to make the long, dangerous trek through the Sierra Nevada mountain range to get back to the Seavers.
Along the way, they have a run-in with a pair of black bear cubs and a larger brown bear (the latter implied to be the cubs' mother), before attempting to cross a river. Sassy tries using some rocks and a rotten tree trunk, but the trunk breaks when she's halfway across and she's swept over a waterfall to her presumed death. Chance and Shadow are forced to go on without her, mourning their loss with heavy hearts. Later, they are attacked by a ferocious mountain lion. Thinking they are doomed, Chance tells Shadow where he hid all the stuff back home, but when he mentioned the seesaw, this gives Shadow an idea. Acting as a decoy, he lures the mountain lion onto one end of a large rock set up like a seesaw, so when Shadow gives Chance the signal, he jumps on the other end, flinging the mountain lion into the river. As the humiliated feline retreats back into the woods soaked to the skin, Chance and Shadow bark in triumph, with Chance taking Sassy's earlier taunt to him of "cats rule and dogs drool" and changing it to "dogs rule and cats drool" as he tells off the mountain lion. Sassy, who had survived the plunge over the waterfall and was nursed back to health by a local hermit named Quentin, hears their barking and heads off to reunite with them. Together again, the three continue onward, but Chance soon tries to befriend a porcupine, and in annoyance, it swats Chance with its tail, leaving several quills stuck in his muzzle. As night falls, they find a little girl lost in the woods, and not able to leave her due to their loyalty as man's best friend, Chance and Shadow choose to stay with her all night, as does Sassy. The next morning, they hear the search party of the girl's parents, U.S. Forest Rangers, and rescue team, and Shadow leads them back to her location, allowing her to reunite with her parents and get medical attention. The rangers then recognize Chance, Shadow, and Sassy from the lost pet posters put up by the Seavers when word came that the pets had left Kate's and were presumably heading home, and take them to the local animal shelter for the Seavers to reunite with them at.
However, once there, Chance believes they've been taken to the pound and panics. While he is taken to the medical room to have the porcupine quills removed, Shadow is taken to be put in one of the cages until the Seavers arrive, while Sassy was able to escape. Sneaking back in, she frees Shadow, and the two of them free Chance from the medical room after the quills have all been removed, and escape back into the woods, unaware that the Seavers were coming to get them.
Soon, they see the city in the distance and realize they are almost back home. Only one obstacle is left for them: the local rail yard. After avoiding being hit by one of the diesel locomotives as it shuffles through the yard with its freight train, Shadow attempts to lead the way again but falls into a muddy sinkhole when the rotted wooden boards over it give way under his weight. Horrified, Chance and Sassy see if he's alright and plead for him to try and climb his way out, but while Shadow initially attempts it, he soon realizes he's too old and gives up, lying down to essentially die right there in the hole. Chance, refusing to let Shadow simply give up, carefully makes his own way down into the hole and begins angrily and tearfully scolding Shadow for giving up when they are so close to home and to give it another shot, but Shadow seems too demoralized to even care and tells Chance he's on his own now. The only thing he has left to do to learn from Shadow is how to say goodbye, but Chance still refuses to leave Shadow behind.
In the end, Chance apparently is shown to have to leave Shadow behind after all and returns home to the Seavers to reunite with Jamie, with Sassy following shortly thereafter. However, Shadow was able to find a second wind, climb out of the hole, and reunite with Peter after all. Chance is amazed when he sees Shadow reunite with Peter, thinking to himself that it seemed that years came off of Shadow when he was reunited with his boy. Happy to be home again, Chance runs back into the house when Jamie calls for him and is last heard shouting with joy at what the main course for dinner is: turkey, ironically the bane of his existence back at Kate's farm.
In the sequel, it is clear that Chance's relationship with Jamie has started to become strained, as when Chance comes into Jamie's room to play, Jamie takes no notice of him while looking for his shoe Chance tossed into the bushes earlier while playing with it. He notices Jamie knock his Barry Bonds autographed baseball onto the floor, and immediately picks it up and starts chewing on it. When Jamie catches him, he takes it back and slams the door in Chance's face. When Jamie then leaves for baseball practice with his team before the Seavers have to catch their flight to Canada for vacation, Chance tries to come with him, but Jamie angrily orders him to stay home. When Chance worries if Jamie is upset with him for something, not understanding why, Sassy sarcastically tells him that Jamie is going to send him back to the pound as punishment. Annoyed, Chance rolls the tube she's in down the driveway until it bumps into the family SUV. Once again mocking Sassy with saying "dogs rule and cats drool", Chance takes off to go after Jamie. When he reaches the baseball field, he soon meets up with several dogs who are commentating on the game and decides to watch the game, but when Jamie's coach sends one shot far into the outfield, Chance can't resist himself and runs out onto the field, grabs the ball, and runs off with it as Jamie and his team chase after him. When Chance finally stops to catch his breath, Jamie is angry at him for not staying home, before one of his older, female teammates orders him to take Chance and go home.
- “I've seen some pretty dumb dogs, Seaver..."
"Excuse me, "dumb"?!"
...Yours is pathetic!"
"All right, that's it!”
- ―Chance retaliates against Jamie's older teammate for insulting him
When she makes the mistake of calling Chance pathetic, angered, Chance grabs at her catcher's glove and, after some effort, finally yanks it away and runs off with it as Jamie and the rest of his team chase after him. Sometime later, Jamie and Chance are heading home, but Jamie is in no mood for games when Chance tries to imitate what he did earlier with Jamie's glove before he wrestles it free and heads for the house with Chance right behind.
- “It's Chance's fault! We chased him all over the park!"
"Aw, come on, Jamie. Don't be mad at me, pal."
"I still don't see why we have to go on a stupid camping trip anyway. I'm going to miss the two most important games...”
- ―Jamie vents his fury at Chance and missing his baseball games to his parents
When they arrive, Bob and Laura are already loading the SUV and are late getting to San Francisco International Airport to catch their flight. Laura encourages Jamie to hustle and get in the SUV, but Jamie, fed up with Chance's behavior, and having had enough of it, finally snaps and angrily blames him for his family's tardiness, disobeying all of his orders, and disrupting the game. Realizing Jamie is furious with him for what he did, Chance tries to apologize, and tells him to go easy on him, but Jamie will have none of it, more concerned about the baseball games he'll miss while they are in Canada. On the way to the airport, Chance also expressed some paranoia as to what the Seavers were up to, especially when giving them a green kibble (implied to be a sedative), before deciding to vomit his up (also vomiting up a blue ball of his that he presumably ate in the past) before singing a variation of 99 bottles of beer on the wall with the others, though Sassy voices her contempt with the song.
When they reach the airport, Chance struggles as Bob tries to get him into his carrier to be taken to be loaded onto the plane, but as the carriers containing him, Shadow, and Sassy are taken to the tarmac, when Bob asks Jamie if he is going to say goodbye to Chance, Jamie, still upset with him for disrupting the game, simply tells Chance "see you later" in a sarcastic tone, making Chance feel all the more worried that Jamie hates him disobeying his orders. When he sees the airport workers in their hazmat suits, he panics, thinking the airport is a dog pound and workers are the dog pound catchers and Jamie is sending him back there because of how bad he's been as punishment. As Chance freaks, he manages to wiggle his carrier, ignoring Shadow's words saying their humans wouldn't do that to all of them and Sassy's pleas to stop, to where it falls off the baggage cart and is split open between two baggage trolleys heading in opposite directions, much to Shadow's horror. Freed, he heads back to the terminal to find Jamie and apologize to him, but by then, the Seavers are already on their flight as it is being moved away from the gate to taxi to the runway for takeoff. Joined by Shadow and Sassy after Sassy got them out of their own carriers, they follow Chance back through the terminal and the baggage area to the tarmac. Unfortunately, they are unsure of which plane carries the Seavers, and Chance tells Shadow to hurry as he spots the airport security forces mobilizing to retrieve them and get them on their flight before it takes off. When Shadow spots the plane he can tell the Seavers are on, he gets the pets dashing toward the runway as the security vehicles are soon in pursuit. When they reach the runway the plane is heading down as it accelerates to takeoff speed, they wait in the hope that the pilots see them and stop, but just as the plane is about to run them over, it reaches takeoff speed and lifts off, leaving the pets behind as the Seavers head to Canada without them.
Having almost forgotten about the airport security vehicles chasing them, as the vehicles screech onto the now clear runway, the pets head for the airport's security fence on the perimeter to escape, unaware the vehicles were only trying to recover them to get them on the next flight to Canada to reunite them with the Seavers. As Shadow and Chance dig their way under the fence in order to escape, Sassy climbs up it and squeezes through the gap between the top of the chain link and barbed wire above it while Shadow is already safely under and through as the security team arrives to recover them, while Chance had gotten his collar snagged on the bottom of the fence, but with Shadow and Sassy's encouragement, Chance gets his collar free and escapes just in time as the security team watches in disbelief at having failed to recover them as they take off into the distance, with Chance taunting them with "give my regards to the bad place, suckers!"
Now with the Seavers on their way to Canada, Sassy reprimands Chance for his paranoia getting them lost again, and Shadow realizes they have to find their way home once more. However, remembering what happened when they did it the first time with heading home through the Sierra Nevada, Chance doesn't want to go through that again but soon is forced to join Shadow and Sassy anyway. Meanwhile, when word of what happened reaches the Seavers in Canada at the airport there, Jamie becomes horrified, thinking this is all his fault due to his earlier anger towards Chance, and Peter and Hope are just as terrified, knowing full well they can't enjoy their camping trip with their pets lost in San Francisco. After some pleading, they convince Bob into having them all return home to find their pets.
Back in San Francisco, after Chance, Shadow, and Sassy make their way through Chinatown and Chance prevents Sassy from getting food from a young boy named Tucker who is caring for his own kitten named Tiger when he scares Tucker back into his house, the pets soon run afoul of Ashcan and Pete. When Riley shows up with his gang, Chance takes off on decoy duty, unaware that Riley and his crew had come to chase off Ashcan and Pete, not back them up. When Shadow and Sassy realize Chance is gone, Riley dispatches Delilah to find him. When she does, it doesn't take long for a relationship to start to blossom between Chance and Delilah. Delilah also explains to Chance how Riley came to form his gang and develop a fear of humans after being left out in the rain-soaked street on Christmas night when he was a puppy after the child he had been given to as a Christmas gift rejected him. Delilah also admits she was born a stray and never had a home herself.
While they are together, they spend some time exploring San Francisco, checking out the sea lions down at the harbor, among other things, before retiring to Riley's hideout in the dockyard. When Riley and his crew return later with Shadow and Sassy after witnessing them save Tucker and Tiger from their house after it caught fire thanks to the discarded cigar from Jack, one of the goons that drive the "Blood Red Van", smoldering and igniting some dry grass next to the house, Shadow and Sassy are furious with Chance, and Riley with Delilah. When Bando nearly gets into a fight with Chance over Delilah being his girlfriend, Riley lays down the law with saying Chance is a pet, a dog with a human owner, and fed up, Delilah takes Chance with her outside to cool off. As Chance and Delilah make plans for going out and about in San Francisco again the next day, things take a turn for the worse. As Sledge and another of Riley's gang are watching Chance as he enjoys chewing on an old tire and a bag of discarded garbage while Delilah watches, they soon spot the "Blood Red Van" entering the area and retreat to cover inside the warehouse were Riley set up shop. However, Chance is too busy with his loot to notice until Jack and Ralph are closing in to capture him as their latest payoff with sending Chance to the lab to be experimented on. While Jack lures Chance with a cheeseburger, Ralph is able to snare him. Upon seeing Chance being captured, Riley gives the order to move out to try and save him. They are too late initially when the "Blood Red Van" drives off, but Riley leads the gang through a shortcut in the warehouses to intercept Jack and Ralph before they can leave the dockyard. On Sassy's suggestion, they form a roadblock to prevent the van from leaving. Jack orders Ralph to run them over, despite Ralph arguing that they would be worth more captured alive, but when Jack becomes insistent with turning them into roadkill, Ralph refuses, resulting in the two of them struggling for control of the van as it moves closer to the dogs. When it gets too close, Riley orders them to scatter, but Delilah holds her ground until she's nearly hit by it. Faking her paw being injured, she enrages Bando enough to where he leaps into the van to attack Jack and Ralph directly, forcing them out to escape his wrath and be surrounded by Riley's gang and Shadow, while Sassy goes to free Chance and the other dogs that had been captured by Jack and Ralph.
- “Before I set you free...Say it!"
"No, not in front of the guys! Alright, cats rule."
"Alright! Cats rule!”
- ―Sassy forces Chance to once again admit that cats rule and dogs drool
After forcing Chance to admit that her old saying of "cats rule and dogs drool" is the truth in the matter at the moment, Sassy frees Chance and the other dogs, who immediately go after Jack and Ralph, who had been kept restrained by Riley and Sledge, while Bando sees to the end of the "Blood Red Van". When it is all over, when Bando asks Delilah about her paw, Chance, oblivious to the ruse, asks what is going on, before Bando tells him off for nearly getting all of them killed because of his actions. Upon Delilah admitting that Riley is right and Chance and she can't be together, heartbroken, Chance leaves. When Shadow tries to stop him, Chance angrily tells him off to leave him alone, clearly furious with him and everyone else for their actions by trying to keep him and Delilah apart and what they said to him, as he says in his face and everyone else’s that he doesn't need him, or Sassy, or Delilah, or anyone else and continues departing, leaving Delilah feeling guilty and ashamed for what she had done and everyone else watches helplessly as he vanished. Riley had his gang go out looking for him, but they were unsuccessful. However, having seen how much Peter and Hope mean to them, Riley agrees to take Shadow and Sassy to the Golden Gate Bridge so they can return home. They reach the bridge by morning, but as Shadow and Sassy make their way towards it, they stop in a construction yard as Shadow feels they can't return home without Chance. Unfortunately, as they both were about to go back to the city to look for him they are ambushed by Ashcan and Pete, but luckily, Chance returns and is able to take down Ashcan and Pete using the same trick he used on Sassy before they left for the airport. With Ashcan and Pete incapacitated, Chance reunites with Shadow and Sassy and they head for the bridge, but Chance is still fearful that Jamie is still furious with him.
Once across the Golden Gate Bridge, they just have to cross one more road before reaching home on the other side of the hill beyond the road, but while Shadow and Sassy cross with no problem, Chance stops partway across to look back towards San Francisco, still torn up about Delilah. Sassy tries to encourage him to come along by mentioning food, but he ignored her and didn’t budge. This results in where he's unaware when a large semi-truck comes around the bend, heading straight for him. Shadow and Sassy shout to Chance to look out as the trucker, seeing Chance, slams on his brakes and blares his horn in warning, as behind him, the Seavers, having returned to California themselves, hit their brakes to avoid hitting the trucker as his rig jack-knifes to avoid Chance, but can't stop quickly on the rain-slick road. As the Seavers' SUV spins out to avoid crashing into the back of the trailer, Bob and Laura check to see if the kids are okay, before Bob prepares to go out and talk to the truck driver. However, that is when Peter and Hope spot Shadow and Sassy and tell Bob and Laura, who are stunned to see the pets made it before Peter and Hope reunite with Shadow and Sassy before Jamie calls out to Chance, but there's no response. As Bob meets up with the truck driver and checks to see if he's okay, when he asks what happened, the truck driver explains that there was a dog in the middle of the road. Bob realizes in muted horror that if Shadow and Sassy were here, then that means Chance was as well, and he probably was the dog the truck driver tried to avoid. After having Laura go talk to the truck driver, hinting that Chance may be involved, to Laura's own horror, Bob goes to talk to Jamie, who asks worriedly where his dog is. Bob, unsure of how to explain it, flat out tells Jamie that the reason the truck driver hit his brakes so hard was that there was a dog in the middle of the road. Horrified in thinking Chance is dead before he could apologize to him for his earlier anger towards him, Jamie runs to the front of the rig, only to hear a whimper come from under the cab. As he leans down to look as Bob and Laura try to stop him, not wanting him to see what they feared could be their worst-case scenario, Chance is revealed to be alive, and unharmed, having ducked down and cowered in fear to avoid being hit by the rig as it slid over him while trying to stop. As Jamie joyfully shouts Chance's name in relief at seeing him safe, Chance, stunned to see Jamie, emerges to reunite with his boy, overjoyed to see him again, and no longer angry with him for his actions, as Jamie apologizes for snapping at him before and voices how much he loves Chance, who returns the thought.
Sometime later, the Seavers are back home, and Jamie prepares to head out to play baseball with his team and called Chance to come along this time, but Chance doesn't seem too interested now like he did in the beginning before they went to the airport, telling Jamie to go on without him. While witnessing that he is still downhearted, Sassy admits that she misses that old Chance. Jamie is worried and asks Bob about it, and Bob assures Jamie that Chance will be fine, unaware that Chance was still suffering from a broken heart over Delilah. After Chance mistakes a dog chasing after its owner on a bicycle for being Delilah, he lies down and, after hearing a second set of barking, tries to tell himself to get a hold of himself and stop thinking about Delilah. However, soon enough, Delilah herself appears at the end of the driveway, to Chance's shock. It turns out, that after a heart-to-heart talk with Riley, Delilah decided to follow her heart and it led her home to Chance (and also briefly barks, confirming the barking he heard earlier was indeed her). She apologizes to him for what she did and said to him. As they reunite, their barking attracts Jamie and the rest of the Seavers along with Shadow and Sassy, at which point the Seavers discover Delilah, and noticing that she doesn't have a collar or tag, marking her as a stray, after some thought and convincing from Jamie (who apparently picked up that Chance's behavior earlier was due to a broken heart), Bob agrees that Delilah can stay, to Chance's joy. As a result, when the pizza man arrives, Chance, his usual excitable self back, runs up to him and soon gets him to drop the pizza, which Chance soon digs into, despite Jamie telling him to stop, and Chance also voicing how hot it is, but he doesn't mind. For him, he couldn't have asked for a better ending.
- In Homeward Bound II: Lost in San Francisco, even though Chance is still called an American bulldog, he was actually portrayed by an American Pit Bull Terrier. This is apparent in that in the first movie, Chance's face was more mushed in, whereas in the sequel, his face was stretched out. American bulldogs have mushed-in faces, while pit bull terriers do not.
- Chance made a special appearance in Disney Sing Along Songs: Pongo and Perdita as Tiler's dog.
- Both of Chance's pranks against Sassy were later used to get his fellow pets out of a jam.
- Chance's prank of using a see-saw as a catapult on Sassy was later used with a rock seesaw to dispose of a Mountain Lion that threatened to eat them.
- Chance trapping Sassy inside and rolling a play pipe towards a garbage can was later used by Chance to defeat Ashcan and Pete with a construction pipe.