Death Race owner R.H. Weyland (Ving Rhames) has been forced to sell the rights to Niles York (Dougray Scott), a British billionaire who acquired the rights by hostile takeover. York reveals he intends to relocate Death Race to the deserts of South Africa as a Transcontinental Race. Before leaving, Weyland arranges Carl Lucas, also known as Frankenstein (Luke Goss), to have surgery to heal the infected and deadly scars on his face sustained from his gruesome crash. With Lucas one win away from gaining his freedom, York threatens to kill him if he wins.
Before his first race, Lucas engages in a fist fight with other racers and his mask is knocked off in the middle of the fight, revealing to his crew who believed him dead. Before the first race, all of the female navigators had to participate in a Death Race “Navigator Wars” and Death Race itself is now hosted and produced by Satana (Hlubi Mboya). Contestants to be chosen are the top 10 survivors, with Katrina (Tanit Phoenix) among the survivors. Before the first race, all racers receive GPS locators surgically so the showrunners can locate the racers are at all times and if necessary kill them if they attempt an escape.
During the first race, racing in the deserts of Africa present a different set of difficulties compared to racing on the Terminal Island prison race course. Eleven racers take the start, but one, Jackal, jumps the start and is killed by the missile tracker. Joker, Pretty Boy and the Tazmanian Devil also die in the first sector. Razor beats out Frankenstein by a hair to win the first race.
After the race, Katrina tells Lucas they cannot resume their previous relationship as she is hearbroken over finding out he kept his survival secret from her. A fight ensues after the first race and Goldberg (Danny Trejo) is cut in the scuffle. The show’s surgeon makes advances on Goldberg and the two establish a relationship. In order to make Katrina jealous, the producer Satana orders Psycho’s (Jeremy Crutchley) navigator Amber to have sex with Lucas, who seems to refuse the offer. Satana and York grow suspicious that Lucas is up to something due to his non-rebellious attitude to being forced to lose. Lucas then explains to his team mates his deal with York to lose and says instead he made a “new deal.”
The second race then commences with the death of three more drivers. Fury is killed after being tricked by Olga Braun (Death Race’s first ever female driver) and she is in turn killed by Razor seconds later. Afterwards, Razor is struggling to handle both Lucas and Psycho before the three are joined by 14K (Robin Shou), having disabled Nero’s car before leaving him to get beaten to death by an angry mob of locals. The race ends with Lucas emerging victorious in the second race. But at that moment, Goldberg is caught in an explosion caused by stray bullets from local hostile war lords, and is pronounced dead. Later on, York reminds Lucas he is to lose his next race to 14K or York will torture him and Katrina. Satana then discovers York wishes to replace her as producer and remove her from Death Race so he can assume complete control. Before the next race, Katrina confesses her love to Lucas, and Lucas admits he did not have sex with the other navigator when he had the chance. The final race begins with Razor disabling Psycho’s car, and Psycho dies in the flames while his navigator Amber survives without taking any damage. Lucas taking the lead and York attempting to kill Lucas with a homing missile but 14K shoots flares to send the missile off course which saves Lucas’s life returning the “life for a life” favor.
Near the end of the race, Lucas holds a commanding lead and kills many of the Death Race guards along the way, vowing to kill York. However, Lucas allows 14K to pass him and then speeds to York. As York attempts to escape, Satana handcuffs him to the table for attempting to replace her also for his actions and making an earlier phone call with a need of help to deal with York. Lucas crashes his car into the control room and explodes, engulfing the room in flames. Initially, it is insinuated that everyone except Lucas perished in the crash. However, it is revealed that Lucas and Katrina escaped unharmed, and now the unrecognizable York as Lucas, aka Frankenstein. In order to assert York is Frankenstein, Lists (Fred Koehler) confirms it is him, along with the show’s surgeon who claims the implanted chip is that of Lucas’s.
It is then revealed that Lucas’s “new deal” he made during the meeting with Weyland was to fake Goldberg’s death; the surgeon Olivia (Kim Syster) (Goldberg’s love interest) falsely pronounced him dead, and after the crash pronounces York and Katrina as dead and Lucas as the sole survivor. Since York is officially dead, Weyland regains control of Death Race and grants Lucas, Katrina, Lists, and Goldberg their freedom, but Lists elects to stay behind and returns to Terminal Island. Weyland pays Lucas a substantial amount of money for his help regaining control of Death Race, he and Katrina relocate with Goldberg elsewhere, and York is punished for his crimes and he is imprisoned in Terminal Island, forcing him to become the Second Frankenstein.