Continuity mistake: After the double train fails to slow train 777 and gets switched to another section of track, in the control room, you see the train has already partly gone around a bend on the TV screen behind the bearded character, then cuts to the TV report footage which shows the train continuing on for a few seconds, though when the scene cuts back to the train, it is only just beginning go around the same bend that it had already partly travelled.
Factual error: Towards the end, when the red pickup is alongside 777 with Colson on the back, the camera shows the speedo of the truck, and the needle going over 60 MPH. This speedo shot is of a 1967 Shelby Mustang GT 500, not a Ford Super Duty. As an aside, this shot is taken from "Gone in 60 Seconds", with Nicholas Cage.
Factual error: In the scene immediately after the locomotives that were trying to slow 777 get derailed and blow up, the next scene immediately shows Colson in the cab of his train exclaiming about the explosion which he sees just over the tree tops. Impossible. Colson's train is still miles away on the head on collision course with 777, and Colson could not possibly see this explosion, let alone as if it was just around the bend.
Continuity mistake: In the big finale where Ned is racing alongside the train in his truck and picks up Colson, they have said that the 777 is at 75 mph and gaining speed toward 80. Yet the view of Ned's speedometer shows him just getting to 70 mph while he is passing the train. To be passing the train he would have to have been in the 90-100 mph range.
Factual error: In the scene where they try to slow the train with 2 engines and lower an engineer aboard, at the end the 2 engines derail as they go onto a siding and explode. Engines like these would never explode in real life, and none have ever done so in any derailment in history. They only contain diesel fuel which is very difficult to ignite, only other cars with flammable materials ever explode in real derailments. In the scene they do not strike anything else with explosive potential, and the explosion is not necessary for the plot. The engineer aboard could likely have died still just from the speed of the derailment.
Other mistake: In the scene when Will finally stops the train, his phone beeps letting him know he has a missed call. He looks at his phone and sees the photo he presumably has associated with his wife Darcy. Later on, during the press conference scene, right after the first part of the dialog between Will and Frank about "corporate", there is a shot of Darcy at the press conference. This exact same shot was the photo used in Will's cell-phone earlier on.
Continuity mistake: Change in the number of cars 1206 is suppose to haul. In the beginning of the film Frank and Will are in a truck with other engineers. Frank asks Will what the daily list is. Will responds that they are suppose to pick up 25 cars. After they pick up the cars and are leaving the yard, Frank notices they have too many cars. He points this out to Will and asks how many cars they are suppose to get and Will says 20 (not the 25 he said earlier) Will says he counted 5 too many cars. Then they talk about the 25 they have that is incorrect it should be 20.
Continuity mistake: When Dewey and Gilleece are attempting to jump aboard the runaway train by driving along side its front cab, the passenger side door is ripped off by crashing into a train signal. In one shot the door is still partially attached to the vehicle and trailing on the ground. But in the next shot the door is gone and nowhere to be seen on the ground behind.