The film was released in the United States and Canada on November 12, 2010, and in the United Kingdom on November 24, 2010. It received mostly favorable reviews from film critics; it garnered a "Certified Fresh" rating on Rotten Tomatoes based upon aggregated reviews, and a rating of "Generally favorable reviews" at Metacritic. The film was nominated for an Academy Award for Best Sound Editing at the 83rd Academy Awards, but lost to Inception.
Veteran Allegheny and West Virginia Railroad (AWVR) engineer Frank Barnes oversees his co-worker, freshly hired conductor Will Colson as they use AWVR locomotive #1206 to run a train outside the fictional city of Stanton, Pennsylvania. Their job is to pick up twenty cars at a zinc processing facility outside of Stanton but Will, who is dealing with personal issues, hooked five additional cars inadvertently.
Meanwhile, down the line near Fuller, Pennsylvania, AWVR hostlers Dewey and Gilleece are ordered by dispatcher Bunny to move a freight train led by locomotives #777 and #767 off its current track. Gilleece notices that the air brakes are not connected but Dewey tells him not to bother connecting them since it is only a short trip. Dewey slows down the locomotive by setting the dynamic braking and leaves the moving cab to throw a misaligned rail switch. But as he does, the locomotive shifts itself from idle to full power, and begins moving down the track on its own. Dewey tries to re-board the locomotive, but falls just as he grabs onto the handrail and is forced to report the train as a "coaster" to Fuller yardmaster Connie Hooper. Connie immediately tells them to chase after it and calls lead welder Ned Oldham, who has not yet shown up at the yard, to go further down track to intercept the train at the nearest siding to 777's last known whereabouts. Ned arrives just as Dewey and Gilleece head to the siding, with the train believed to be due into the area as it is still supposed to be coasting. However, Dewey reveals to Connie that he left the cab with the throttle at full power. Because of this, Connie realizes that 777 is not a coaster but a runaway train. She tells Dewey and Gilleece to catch up to the train before it reaches a split in the track and try to climb on board while Ned is dispatched to resume his pursuit. Dewey and Gilleece are able to reach the train, which by the time they catch it is running at 70 miles per hour. They manage to align their high-railing truck with the train, but just before Gilleece could board, the door hits a railroad signal in between the two tracks and almost breaks it off, making them unable to board the train from their truck.
Connie reports the runaway to Oscar Galvin, vice-president of operations for AWVR, and coordinates with local police, sheriffs, and Pennsylvania State Police to ensure all grade crossings along the line are secured. Visiting Federal Railroad Administration safety inspector Scott Werner, who was scheduled to speak to a group of school children, alerts them that the molten phenol being carried by eight tanker cars, plus the diesel fuel in the locomotives, on the train poses an immediate danger. Meanwhile, the runaway 777 has become a massive media event as television stations across Pennsylvania have picked up on the story.
Connie, aware that the train is heading toward a stretch of the main line that runs through a fairly highly populated area, suggests that the train be purposely derailed in a stretch of unpopulated farmland before it reaches the towns. Galvin, however, rejects the idea out of concern for the massive financial loss AWVR will take rather than the lives of innocent people that could be lost if the train should happen to derail. Instead, AWVR comes up with is own solution: a lashup of two engines, #7375 and #7346, driven by 26-year veteran engineer Judd Stewart is sent ahead of the runaway at a slower rate of speed, with the belief that the lashup will force 777 to decelerate once it makes contact. Once that happens, AWVR employee and U.S. Marine Ryan Scott is to rappel from a helicopter onto the train and climb into the cab to take control. Things seem to go well as Stewart was able to slow down the runaway train and Scott is lowered onto the locomotive, but just as he puts his feet down on it, 777 suddenly begins to shove the lashup again, causing Scott, still connected to the cable leading from the helicopter, to be pulled back from the locomotive and crash into the windshield of the second locomotive, #767, which nearly kills him. After this happens, Scott is lifted back into the helicopter, unconscious, as Stewart tries his best to slow the train down again, but 777 keeps on pushing the lashup faster. Then they try to abort the attempt by having the lashup go into a siding, but 777 bumps into the lashup again, causing the two diesels to jump the rails and crash just as it goes into the siding, exploding into a fireball that kills Stewart. 777 continues on, and the major concern becomes what could happen once the train reaches Stanton; the main line includes an elevated curve that cannot be navigated at that high a speed (dubbed the 'Devil's Curve', due to its sharp curvature and limit of fifteen miles per hour): should 777 hit the curve, it will derail there and cause a massive disaster that could result in the destruction of the whole town and beyond.
As 1206 heads towards Fuller, Frank radios into the yard. Earlier, 1206 found out about 777 being in its path and was still operating under the belief that the train was a coaster. Connie informs Frank that the situation is now much worse than he had known. Frank had been commanded to pull off the track and into a siding several miles back but due to Will's earlier error, 1206 could not fit onto the siding and was forced onto a Repair-In-Place track further along the line. They make it into the RIP siding track as the runaway speeds past them, smashing through the rear car. As it passes, Frank notices that 777's rear car has an open knuckle. He gets out of the cab and unhooks 1206, telling Will that if they go long hood forward toward 777, they could connect to the rear car and properly slow the train enough to where it can pass through the curve in Stanton without major damage.
Frank tells Connie of his plan but Galvin, who has been listening, tells him that AWVR plans to use a derailer near Arklow, a town along the route where 777 is headed next. Frank informs Galvin that the plan will not work, as 777 is too heavy and too fast to derail now. Unmoved, Galvin threatens to fire the engineer and conductor of 1206 if they proceed. Frank then reveals that he has already been fired; being forced into an early retirement by AWVR with half benefits, he admits to have nothing to lose.
Outside of Arklow, Police try to hit the fuel shutoff button with their M16s as 777 passes their grade crossing. They fire several rounds off before ceasing fire at the risk of hitting the diesel fuel tank next to the button. As Frank foresaw, Galvin's plan to derail the train outside Arklow fails as the train blows right through the derailers and sends shrapnel shooting into police cars parked by the tracks. Galvin is left dumbfounded by the failure of the derailers and has no choice but to rely on Frank and Will. Meanwhile, the area around the curve in Stanton is evacuated as 777 approaches as Ned continues his pursuit of the runaway with his police backup.
1206 finally catches up with 777 and Frank and Will are able to hook onto 777's rearmost car despite Will's foot slipping in-between the coupling at first. Though 1206's dynamic brakes begin to reduce the speed of 777, the train is still moving too fast for the curve. Initially they manage to slow down the train but accelerate again since the train is too heavy and they are being dragged behind it. Frank goes out and begins to engage each car's manual brakes in a last ditch attempt to slow 777 down as it nears the curve, eventually planning to get into the cab and stop the train there. Things turn for the worse again when Will sees 1206's load ammeter going from motoring to zero in just a few seconds, and then suddenly to full braking in just one second, causing the locomotive's dynamic brakes to blow out and the runaway 777 to pick up speed again dragging 1206 with it. Meanwhile, Will uses 1206's independent brake to keep the train on the rails as it speeds through the curve. As it does, it leans dangerously to the side, causing a load of pipes to fall off one of its two bulk-head flatcars and land dangerously close to the large gas tanks. The locomotive even takes out a few electrical power poles, but it eventually makes it through the curve. But although the train makes it through the curve without falling from the track, 777 is still out of control and Frank encounters a gap in between one of the tankers he's standing on top of and the bulk-head flatcar that still has its load of pipes that is too wide to cross and thus cannot get to the cab. To make matters worse, the whole train is headed toward Stanton's yard near the end of the line; any one of its switch tracks will derail the locomotives and contaminate the entire yard.
Ned arrives in his truck, and pulls onto a parallel road next to the line. Will jumps onto the truck, and is driven to the front of the train, where he jumps into 777 and is finally able to stop the train. Frank, Will and Ned are celebrated as heroes, and the two reunite with their families. A pre-credit montage reveals the futures of the characters: Frank was promoted and is now retired with full benefits; Will is expecting a second child with his wife; Connie was promoted to Galvin's job; Ryan Scott recovered fully from his injuries; and Dewey is now working in the fast food industry. It is unknown what happened to Galvin after the events, but it is possible that he was fired from the railroad for how he mishandled the events.
- Denzel Washington as Frank Barnes, a veteran railroad engineer
- Chris Pine as Will Colson, a young train conductor
- Rosario Dawson as Connie Hooper, a train yardmaster
- Lew Temple as Ned Oldham, a railroad lead welder
- Ethan Suplee as Dewey, a hostler who accidentally instigates the disaster
- Kevin Dunn as Oscar Galvin, vice-president of AWVR train operations
- Kevin Corrigan as Scott Werner, an FRA inspector who helps Frank, Will, and Connie
- Kevin Chapman as Bunny, a railroad operations dispatcher
- T. J. Miller as Gilleece, Dewey's friend, also a hostler
- Jessy Schram as Darcy Colson, Will's estranged wife
- David Warshofsky as Judd Stewart, a veteran engineer who dies in an attempt to slow the runaway
- Victor Gojcaj as Groundman, a railroad ground specialist
- Meagan Tandy and Elizabeth Mathis as Maya and Nicole Barnes, Frank's daughters who work as waitresses at Hooters
- Ryan Ahern as Ryan Scott, a railway employee and US Marine veteran of the war in Afghanistan who attempts unsuccessfully to board the runaway from a helicopter
- Aisha Hinds as Railroad Safety Campaign Coordinator
- Jeff Wincott as Jesse Colson, Will's brother who helps him on his family situation