Lewis Shaler (Dougray Scott) is a doctor and single father heading home with his young son Max (Joshua Kaynama) on a late night train from London. Max accidentally causes fellow passenger Sarah Barwell (Kara Tointon) to spill coffee on her coat, prompting Shaler to apologize to Barwell. The interaction is the beginning of a romantic connection between the two.
Later, while the train is stationary, Shaler notices an unidentifiable man tampering with the train's brakes. As the train begins to move again he sees another man crawling across the tracks. On investigation, Shaler discovers the conductor has vanished.
Soon after, as the train approaches Shaler's home station, Barwell kisses Shaler and asks him to call her, however Shaler is distracted by the train bypassing his stop. Shaler tries to contact the driver via the intercom, but the driver only speaks to ask how many passengers are left on board. Shaler and fellow passenger Peter Carmichael pull numerous emergency brake cords to no effect. It dawns on Shaler and Carmichael that the driver intends to kill himself and his passengers and, along with fellow passenger Klimowski (who Carmichael originally suspected of involvement), attempt unsuccessfully to stop the train using the rear hand brake.
Later, the train collides with a vehicle at a level crossing as the train is traveling too fast to activate the gates and lights. It kills all the occupants inside instantly and fiercely jolting the passengers. The crash also causes one of the six remaining passengers to suffer a heart attack, and Shaler is unable to revive her. Klimowski and Shaler then work together in an attempt to break into the drivers compartment using a fire extinguisher as battering ram, but their effort is unsuccessful due to the reinforced door.
Klimowski attempts to decouple the train carriages by climbing outside, but this dangerous gambit is cut short by an approaching single-track tunnel. Shaler saves Klimowski by pulling him back on board a moment before the open door's impact with the tunnel. It transpires that the police have laid an ineffective blockade in the tunnel which only momentarily stops the train, and none of the passengers can open the doors due to the narrowness of the tunnel.
Suspecting that they are now close to a destructive collision with the Hastings station buffers, Shaler creates an improvised explosive using the last remaining fire extinguisher. The explosion causes enough damage for Shaler, with help of Carmichael, to de-couple the carriages, however Carmichael falls through the gap in the carriages and is killed instantly. The burning carriages separate as they speed through a suburban station where police officers watch helplessly as the train rushes through with the end car trailing not too far behind. Shaler is left on the front car whilst, Klimowski and Barwell attempt to stop their own carriage with the hand brake at the rear. With the train continuing to burn around him, Shaler takes a moment to compose himself, before running and leaping from the carriage as it explodes, dislodging the driver's hand from the dead man's handle and immediately engaging the brakes. The front carriage of the train finally screeches to a stop just in front of the camera and shows the headlight going off for good.
Shaler is discovered alive and conscious by Barwell, Max and Klimowski while a helicopter circles over the burning wreckage of the train in the distance. The identity of the driver and his motivations for committing a murder-suicide are left unknown.