Continuity mistake: When Del comes out of the passenger side of the dairy truck, he is seen with a black eye, for no reason. The next scene, it is not there. It is there again when he admits to being homeless.
Continuity mistake: When John Candy and Steve Martin are travelling from Jefferson City, Missouri to St. Louis they are seen crossing the Mississippi River to enter downtown St. Louis. This would not have been possible unless the bus driver overshot the entire city and ended up across the river in Illinois.
Suggested correction: I agree with the original post, however There could be several possibilities to this scenario. 1. Road Closures, 2. Road Construction, 3. Accidents, 4. Detours and 5. Heavy "holiday traffic" could have factored into the bus having to enter St. Louis from the east in spite of traveling west from Kansas.
Continuity mistake: When John Candy is singing "The Mess Around" in the car, the car swerves, and a hubcap from the passenger side rolls off. The hubcap is back on in the next scene. (00:57:20 - 00:58:50)
Revealing mistake: Near the end of the film, when Neal is on the final L train home, we see the train pull away from the station. When Neal returns to the station to find Del, the footage of the train leaving is played backwards - you can briefly see a man walking backwards at the top left of the screen.
Factual error: At the beginning of the movie, Steve Martin is trying to catch a cab to LaGuardia at about 5:30PM. In the movie, it's still daylight, whereas in reality, NYC is pitch black by that time of day - the sun sets at about 4:30PM in late November.
Revealing mistake: When the couple is yelling to Del "you're going to kill someone" because he's driving on the wrong side of the interstate, you can see that their car's transmission is in PARK. (00:59:35 - 01:01:05)
Continuity mistake: During Neal's family eating dinner, the kid who says "I prefer noogies" is holding a fork in his hand. When it cuts, the fork is suddenly on the table. (00:06:30)
Continuity mistake: In the driving scene from St. Louis to Chicago, Del is having a hard time taking off his parka in the car. After he spins out of control his parka is half off when Neal says "It's getting hot in here, you should take your parka off." The next shot you see them driving away and Del's parka is on again. (00:33:15)
Visible crew/equipment: When Steve Martin and Kevin Bacon start racing towards the cab, as Bacon starts running, watch carefully as he passes the second window. You can see the camera man sitting on some moving trolley reflected in the window. (00:03:10)
Continuity mistake: When Steve Martin gets off of the train in Chicago near the very end of the movie to search for John Candy in the depot, the part of his hair is on the opposite side (left) from where it normally is. There is no apparent wind blowing his hair - it looks neatly parted on the "wrong" side. When he enters the depot, the part in his hair is back to the "correct" side. (01:23:30)
Continuity mistake: When Del pulls out his wallet and shows his shower curtain rings to Neal, we can see Del's sleeve is pulled up exposing his watch and most of his wrist. When it cuts, the sleeve covers his watch and wrist. (00:09:50)
Continuity mistake: When the boss puts his hands on the table at the beginning, between shots they go from being spread apart to very close together.
Continuity mistake: In the beginning when Neal's boss is looking at his work there is a wide shot showing the man sitting in front of Neal writing on his paper. When it cuts to facing the man he isn't writing anymore. (00:01:10)
Continuity mistake: When Owen arrives at the hotel to meet Neal and Del to drive them to the train station, Owen is wearing gloves on both hands. As he introduces himself and shakes their hands, Owen's right hand is now bare even though there wasn't enough time to remove the glove. (00:33:55)
Continuity mistake: In the beginning when Neal's boss is done looking at Neal's work and is about to state his opinion, we see him holding his glasses in his hand while stretching it out. When it cuts from behind him the glasses are no longer in his hand but he has them hanging from his mouth. (00:01:30)
Continuity mistake: When Neil is telling Del that he thinks it would be better if they traveled separately, the length of Del's cigarette changes (it loses about an inch after a two-second cutaway to Neil then back to Del).
Continuity mistake: When Neal and Del are sitting at the counter eating breakfast at the Braidwood Hotel, talking about how they were robbed the night before, watch the plate of food in front of Neal. The food on the plate changes completely.
Continuity mistake: When Dell and Neal get dropped off to catch the train, there is a shot of the town they depart from. Later in the film, when their burned-out car is impounded, they catch a ride on a semi carrying dairy products, departing from the same town.
Revealing mistake: During the scene where Neal is trying to board his flight from New York to Chicago, the camera pans out to show a shot of the whole airport. But, you can see that the shot was taken in O'Hare airport, in Chicago, but he's supposed to be in New York at that point in the film.
Factual error: If they are really in the Wichita, Kansas airport, listen carefully to the airport announcements (real faintly in the background). When they say for "Mary Ellen" to meet her party upstairs, there's a slight problem with that. There is no upstairs in the Wichita airport. (00:12:53)