About five years after the events of the first film, Dominic and his new crew (Letty, Han, Leo, Santos and Cara) have been hijacking fuel tankers in the Dominican Republic. When their trail gets too hot, Dominic disbands the crew. However, he is later informed that Letty has been murdered. Dominic returns to Los Angeles where he finds traces of nitro-methane at the crash site, and tracks the buyer of the gas to David Park. Meanwhile, Brian O’Conner, who has been working as an FBI agent, is tracking down a drug trafficker named Arturo Braga. When Brian and Dominic cross paths at David Park’s apartment, Dominic is about to drop David out the window. But Brian intervenes, and works a scheme where he enters a street race where the winner would join Braga’s team of drivers. Although Dominic wins the four-car race by bumping Brian’s car, Brian later joins the team by replacing one of Braga’s other drivers.
The team meets Fenix Calderon (Laz Alonso) who directs them to drive the heroin across the border using underground tunnels to avoid detection. Brian realizes that the drivers are to be killed following the mission, and when Fenix reveals to Dominic that he killed Letty, Dominic detonates the nitrous in his car, blowing up a bunch of vehicles. In the chaos, Brian hijacks the Hummer that is carrying the heroin. Dominic and Brian drive back to Los Angeles, hiding the heroin in an impound lot. When Dominic learns Brian was the last person to contact Letty, he attacks him until Brian reveals that Letty was working undercover for Brian, tracking down Braga in exchange for clearing Dominic’s name. Brian negotiates with the agency to free Dominic if they can lure Braga into personally coming to exchange the heroin for cash. However, at the drop site, it is revealed that the Braga they arrested was a decoy, and that the real Braga (John Ortiz) has escaped, fleeing to Mexico.
Suspended from duty, Brian joins Dominic to go to Mexico and in hopes of catching Braga. Although Braga agreeably surrenders, they are pursued by Braga’s men through town and then the tunnels. Fenix T-bones Brian’s car right outside the tunnel exit, but before he can kill Brian, Dominic drives into Fenix. As the police arrive, Dominic refuses to escape, saying he is tired of running. Despite Brian’s request for clemency, the judge sentences Dominic to 25 years to life. During the prison bus ride to Lompoc penitentiary, Brian and Mia, along with Leo and Santos, arrive in their cars and intercept the bus.