In the train yard at dawn, Casey Jones is sleeping in the cab wearing his robe and sleeping cap. He gets changed in his engineer outfit getting ready to deliver the mail (of course, he's in a hurry while doing so). Once the car is finished loading, Casey starts up his engine at a rather fast speed before the conductor could call all aboard. After going through a series of track switches, Casey Jones barely makes it out of the train yard passing two other trains going opposite directions.
Back in the cab, he is seen cleaning the dust off of the coal, and putting it in the boiler one piece at a time. His peace is soon interrupted, however, when the train is covered in a flood caused by rain, which makes Casey "eight hours late." Paddling with his shovel through the water, Casey finally makes it out of the rain and back on the track.
However, just as the train resumes speeds, Casey spots a brown cow on the track and brings the train to a screeching halt. Casey replies "What now, brown cow?" as he complains he is running late and orders the cow to shoo off the track. Once the cow leaves, the train resumes it's fast speed and Casey checks his stop watch again, noticing time elapsed because of the cow problem. So Casey loads more coal with his shovel into the fireplace to make up for lost time.
But once again, Casey Jones encounters yet another obstacle, this time a damsel in distress, tied up on the tracks by a crook with a handlebar mustache. Not wanting to stop again after before, Casey runs up to the front of the engine, but stands on its cowcatcher, and saves the lady. Still not stopping, Casey continues at a fast pace and drops the female off at the next station where a porter runs up and grabs her and thinks that she's a she-mail.
Now with even less time than he thought he had, Casey speeds up the train some more with more coal, now entering and later exiting a snowy plains area, into a dark canyon as if time seemingly flies by quicker than we think. Unknown to the engineer, a madman "who's not on the level" sets explosives on a bridge and just as Casey's train is about to cross, they detonate and send the whole train falling down. Once again, having been undaunted by a seemingly impassable obstacle, Casey's engine doesn't give up, struggles to huff and puff up the other side of the mountain's gorge, and continues on its way once again.
As the train heads on, a gang of train thugs lurk in the shadows, and watch the train from above, because they think that there is gold on that engine, so they charge down toward the train. Still shoveling coal, Casey doesn’t notice that the robbers are now in the engine, guns drawn, until one is nearly shoveled into the furnace. Angered by this new interruption, Casey attacks the gang with his shovel. He continues to battle the bandits almost nonchalantly as he keeps on shoveling more coal into the engine. He successfully beats the gang, but is alarmed to see how late he is when he looks at his watch, then opens the throttle so widely that he snaps it off its ribbing, and throws it away.
Desperate to make it on time, Casey shovels the coal into the furnace crazily, causing the engine to overheat. After running out of coal, Casey throws anything he can into the furnace, still overheating until gears and gauges explode. As the engine begins to fall apart, with Casey trying to hold it all together, the tracks melt while Casey gives his engine some repairs with the train seen roaring down a hill. While otherwise occupied, the brave engineer doesn’t notice another train coming toward him on the same track. Casey’s train is heading toward it like a bullet, and the conductor of Casey’s train runs up toward the engine to warn Casey, but Casey can’t hear him, and the trains collide in a cloud of black smoke.
The mailman waiting at the station thinks Casey is not going to make the stop today, when all of a sudden, the last remaining pieces of Casey’s engine appear, with Casey holding the mail. According to Casey’s watch, Casey made it “On Time…Almost.”
- In the real wreck, Casey Jones does not survive; however, he is the only casualty in the crash, and has saved untold numbers of lives that day. In the cartoon wreck, when he is on a collision course with another train, Casey survives the wreck after some works on two 4-8-0s Nos. 77 and 5, two engines, with a freight train. This was most likely intentional as showing his actual death would have been much too dark and traumatizing for children.
- The engine on the train in the cartoon that Casey pilots is a 4-4-0 engine or an American type steam locomotive No. 2. These engines of this most common wheel arrangement, a total of which 25,000 were built, were used most common on American railroads, during the 1800s and 1830s and were given the name "American" in 1872 until 1928. In reality, Casey was driving a 4-6-0 Ten Wheeler type engine, Illinois Central Railroad No. 382, on his fateful trip. The original #382 was scrapped in July 1935, but another 4-6-0 ten-wheeler is currently on display at the Casey Jones Home & Railroad Museum in Jackson, Tennessee in place of the #382.
- No. 2 and other types of engines, that have 4-4-0 wheel arrangements, have eight wheels, such as four leading wheels, four drive wheels, and no trailing wheels.
- No. 382 and other engines have ten wheels, such as four leading wheels, six drive wheels, and no trailing wheels.
- In the video game Epic Mickey 2: The Power of Two, the Spirit of the Cartoon Wasteland bears a resemblance to Casey Jones. He also makes announcements when the players enter one of the train stations.
- He appears in the episode "New Shoes", while driving Casey Junior, and riding with Dumbo, Timothy, and the Crows.