Getaway driver Carl "Luke" Lucas attempts to rob a bank for his crime boss Markus Kane. During the robbery, two officers coincidentally enter the building. Luke tells his accomplices to abort, but they refuse; Luke intervenes, but it results in the death of one of the robbers. Luke kills an officer and dumps off his accomplices to fulfill Markus's wishes. Luke is captured following a chase and sentenced to prison. Six months later, he is transferred to Terminal Island.
Terminal Island is a private prison under the control of the Weyland Corporation, which hosts the Death Match, a televised pay-per-view competition where two dangerous convicts are forced to fight to the death or submission. The prisoners are given access to weapons or defense items to use during the fight by stepping on a marked plate in the arena. Luke meets the men who eventually become his pit crew in the Death Race: Lists, Goldberg, and Rocco. The host of the Death Match is September Jones, a former Miss Universe who lost her crown due to allegations of having a sexual relationship with all of its judges. She now works for Weyland Corp to create profit from the pay-per-view subscribers of the Death Match.
Markus puts a bounty of $1 million on Luke's head and convinces some of the prisoners to kill him. Meanwhile, Jones comes up with a plan to boost their profits by converting the Death Match into a "Death Race", where the contestants will have to race over days to win each match. Whomever manages to win five races will be released from prison, originally credited as Weyland's idea. Luke joins the race, during which other prisoners try to kill him to earn Markus's bounty. The female convicts are brought back to play navigator for each racer, and Katrina is paired with Luke.
After winning the first race, Luke is congratulated by R. H. Weyland, the boss of Weyland International, and is paid a visit by Katrina. The two share their feelings for each other and have passionate sex. Later, Katrina is brought to Markus, who offers her freedom if she kills Luke within 48 hours.
During the second race, Luke intervenes in an altercation between two other racers, and saves 14K, who is a member of the Triads. As a result, 14K claims to be indebted to Luke. Later in the same race, Katrina warns Luke that Markus offered to buy her freedom if she would kill him. They suddenly find out that their own car was sabotaged by one of Luke's pit crew members, so Luke saves Katrina's life by ejecting her from the car, which crashes after being hit with a heat seeker missile fired by Big Bill (who is later killed by his navigator after he accidentally killed his pit crew); Katrina and Luke's pit crew arrive and try to save him, but it is too late and everybody, including Markus, is led to believe that Luke is dead. In reality, he survives with extensive scarring to his face. He joins the race as the new character "Frankenstein", with a mask to hide his identity.
As the last race begins, a Triad assassin sent by 14K raids Markus's mansion and executes Markus as a favor to Luke. Lists kills Luke's pit crew member Rocco who tampered with Luke's car, and Luke kills September by running her over with his car, before he races with the other competitors.
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