Jamie was first seen attending his parent's wedding, where his brother, Peter Seaver hands him a frog and he gives it to their sister, Hope Seaver, who then freaks out and drops the frog on the ground and Jamie bursts out laughing. They then hear a crash noise coming from inside the house, nearly interrupting the wedding and Shadow Peter's pet dog growls at the noise. It turn out it was only a lampshade being knocked down by Chance who was been annoyed by Sassy Hope's pet cat, but they ignore the noise coming from the house and continue the wedding. While playing some balloons with Peter and Shadow, Jamie witnesses Sassy being catapult into the sandbox by Chance and he and Peter burst out laughing at Sassy's misfortune, causing Hope to call Chance a stupid dog and reports it to their mother.
After the wedding, Jamie and his family go to the farm owned by their friend Kate, where they leave Shadow, Chance, and Sassy to be looked after her ranch's hand Frank. Before leaving Jamie plays Frisbee with Chance until his father throws it and Chances catches it for him.
A few days later, Jamie later received a word from Kate and Frank that Chance, Shadow, and Sassy are no longer with them anymore due to them returning back home, but could be lost somewhere in the woods trying to cross the Sierra Nevada mountains. He and Hope are crying at hearing this, while Peter was upset and harshly scolds their father for leaving them at the farm and refusing to go look for them.
Later, Jamie was at school practicing for a play, when his family arrives informing him that the forest rangers who they sent to look for their pets, finally found Chance, Shadow, and Sassy, who helped a lost girl name Molly find her parents and they are in the shelter with Chance getting medical treatment due to his muzzle getting pinned by a porcupine earlier, to his delight and accidentally drops the pumpkin he was holding, breaking it, and his father apologizes to his teacher for the pumpkin and will replace it.
However when they finally arrived at the shelter, Chance, Shadow, and Sassy already escaped due to Chance mistaking the shelter for a pound and the shelter staff apologize to them for failing to stop Chance, Shadow, and Sassy from escaping and watch Peter calling for Shadow in the rain-filled darkness before returning back home.
Near dusk, Jamie was playing basketball with his father, Peter and Hope, he hears barking in the distance and calls out where the barking is coming from. It was Chance and they reunite followed by Sassy, except for Shadow, who has fallen into a muddy pit at the train yard and Peter laments that Shadow is too old to make it. But Shadow appears in the distance limping (having injured his leg from the fall and how he able to get out of the muddy pit is not revealed) and Peter was happily reunited with Shadow. After being reunited with their pets, they all go inside to enjoy their dinner.
Jamie has grown older, turns seven years old, and lives in San Francisco with his family and is packing some of the luggage to spend their vacation in Canada. Jamie was having trouble with Chance after he stole his shoe and begins looking around the house for it, not knowing it was thrown into the flowers near the driveway by Chance and looks for it in his bedroom. Then Stacey, a friend of his, calls him from the window that they are going to play baseball and he calls to her that he will be there as soon he find his other shoe. Chance enters his room calling to him, but he ignores him and begins looking under his bed. Chance picks up Jamie's Barry Bond's autograph baseball, but Jamie grabs it back, telling him no as it is his baseball that’s been autographed by Barry Bond and slams his bedroom door. Jamie finally gives up of finding his other shoe and instead wears another one and tells his mother that he needs to play baseball and she tells him to back in twenty minutes and not to be late so they can catch their flight. As he was on his way to the park where the baseball game and his friends are waiting for him, Chance chases after him, but Jamie orders to him to stay home and goes on, still upset with Chance regarding both his shoe and his autographed baseball.
But as he arrives and joins his friends playing baseball, Chance follows him after a small talk with Sassy. One of Jamie's friends hit the baseball hard sending it flying some distance, and Chance grabs it and they chase him around the field. Jamie angrily scolds him that he told him to stay away from the field and one of his friends orders him to get Chance back home and calls him a pretty dumb dog. Insulted, Chance grabs her baseball glove, causing her to call Chance a stupid dog while struggling against Chance's grip and trying to prevent Chance from taking it. But Chance is able to grabs it and runs away with it, with Jamie and his friends chasing him throughout the park.
When they finally return home, his mother tells him that they're late and need to get to the airport and he furiously tells her that it was Chance's fault and he and his friends chased him throughout the park. Chance, now knowing Jamie is really mad at him, feels ashamed and guilt-ridden, but Jamie doesn't care, as he's more upset about missing a couple of his baseball games rather than make up with Chance and boards on the car with Chance riding in the back with Shadow and Sassy.
At the San Francisco International Airport, Jamie and his family put Chance, Shadow, and Sassy in their cage before they all could board to the plane. When Bob asks Jamie to say goodbye to Chance as the pets are taken to be loaded into the plane's cargo hold, Jamie sarcastically calls to Chance that he will see him later while Peter and Hope call out that they will met in Canada as the airport workers brings them to the plane's cargo hold where also Jamie and his family will be. Chance fears that Jamie is so upset with him that when he sees the airport workers in their hazmat suits, he fears Jamie is sending him back to the pound and panics, terrified of going back because he upset his owner so badly.
However, when Jamie and his family arrived in Canada, they received word that Chance, Shadow, and Sassy had somehow escaped from the plane due to Chance escaping his cage mistakenly again thinking that he and the others will be take to the pound and also mistook the airport for also being a pound. Learning of the pets being lost somewhere in San Francisco causes Jamie to become guilt-ridden, knowing he's to blame because of his earlier anger towards Chance.
A few days passed at their rented home, and Bob calls the San Francisco authorities to look for Shadow, Chance, and Sassy which they will and also need to watch out for some crooks who are trying to steal some dogs named Jack and Ralph and bring them to their lab. They then board their rented car, ready to return to the airport. At the airport, Jamie was worried about Chance, because he's somewhere in San Francisco with Shadow and Sassy and asked his mom if he will he see him again and she replies that they found their home like what happened before and can do it again. He then apologizes for being a jerk lately and falls asleep with Laura saying that they will be back home soon.
When they finally return to San Francisco, his father hoped that Chance, Shadow, and Sassy are already at home. While on the way home, a semi truck which was in front of them, suddenly skidded to a stop and his father was able to avoid it by stopping their car. Peter then asked what happened and he replies there must have been an accident. They then saw Shadow and Sassy coming down the hill nearby. The truck driver apologizes to the Seavers and asks them if they are okay and Bob replies that they are fine and asks what happened. The truck driver replies that there was a dog in the middle of the road. He tried to stop, but the road was slick with rain so his rig couldn't stop as fast as he had hoped. Bob, fearing the worst in knowing it was Chance if Shadow and Sassy were there, has Laura speak to the truck driver while he speaks to Jamie. When he explains what happened, Jamie, horrified in thinking Chance had been killed before he could apologize to him, runs to the front of the truck to know for sure. They found Chance, who was in the middle on the road safe and sound, having cowered in fear and ducked down to avoid being hit and was still cowering until he sees Jamie, at which point he comes out and reunites with Jamie, who apologizes profusely for his earlier anger towards Chance and admits he loves him.
Back home, Jamie and his family meet and adopt a new dog named Delilah, Chance's love interest whom Shadow, Chance, and Sassy met in San Francisco while on their way back home and dealing with Ashcan, Pete, Jack, and Ralph.