When Dominic "Dom" Toretto (Vin Diesel) is being transported to Lompoc prison by bus, his sister Mia Toretto (Jordana Brewster) and friend Brian O'Conner (Paul Walker) lead an assault on the bus, causing it to crash and freeing Dom. While the authorities search for them, the trio escape to Rio de Janeiro. Awaiting Dom's arrival, Mia and Brian join their friend Vince (Matt Schulze) and other participants on a job to steal three cars from a train. Brian and Mia discover that agents from the U.S. Drug Enforcement Agency (DEA) are also on the train and that the cars are seized property. When Dom arrives with the rest of the participants, he realizes that one of them, Zizi (Michael Irby), is only interested in stealing one car, a Ford GT40. Dom has Mia steal the car herself while he and Brian fight Zizi and his henchmen, during which Zizi kills the DEA agents assigned to the vehicles. Dom and Brian are captured and brought to crime lord Hernan Reyes (Joaquim de Almeida), the owner of the cars and Zizi's boss. Reyes orders the pair be interrogated to discover the location of the car, but they manage to escape and retreat to their safehouse.
While Brian, Dom, and Mia examine the car to discover its importance, Vince arrives and is caught trying to remove a computer chip from it. He admits he was planning to sell the chip to Reyes on his own, and Dom forces him to leave. Brian investigates the chip and discovers it contains details of Reyes' criminal empire, including the locations of US$100 million in cash.
Following the murder of the DEA agents aboard the train, blamed on Dom and his team, DSS agent Luke Hobbs (Dwayne Johnson) and his team arrive in Rio to arrest Dom and Brian. With the help of local officer Elena Neves (Elsa Pataky), they travel to Dom's safehouse, but find it under assault by Reyes' men. Brian, Dom and Mia escape, and Dom suggests they split up and leave Rio, but Mia announces she is pregnant with Brian's child. Dom agrees to stick together and suggests they steal Reyes' money to start a new life. The trio organizes a team to perform the heist, recruiting Han Seoul-Oh (Sung Kang), Roman Pearce (Tyrese Gibson), Tej Parker (Ludacris), Gisele Yashar (Gal Gadot), Tego Leo (Tego Calderón) and Rico Santos (Don Omar). Vince later joins the team after saving Mia from being captured by Reyes' men, earning Dom's trust once more.
Hobbs and his team eventually find and arrest Dom, Mia, Brian and Vince. While transporting them to the airport for extradition to the United States, the convoy is attacked by Reyes' men, who kill Hobbs' team. Hobbs and Elena are saved by Dom, Brian, Mia and Vince as they fight back against Reyes' men and escape, but Vince is shot in the process and dies. Wanting to avenge his murdered team, Hobbs and Elena agree to help with the heist. The gang breaks into the police station where Reyes' money is kept and tear the vault from the building using their cars, dragging it through the city with police in pursuit. Believing they cannot outrun the police, Dom makes Brian continue without him while he attacks the police and the pursuing Reyes, using the vault attached to his car to smash their vehicles. Brian returns to kill Zizi, while Reyes is badly injured by Dom's assault. Hobbs arrives on the scene and kills Reyes. Hobbs refuses to let Dom and Brian go free but, unwilling to arrest them, agrees to give them a 24-hour head start to escape. The gang splits Reyes' money, leaving Vince's share to his family, before the members go their separate ways.
On a tropical beach, Brian and a visibly pregnant Mia relax. They are met by Dom and Elena. Brian challenges Dom to a final, no-stakes race to prove who is the better driver.
In a post-credits scene, Hobbs is given a file by Monica Fuentes (Eva Mendes) concerning the hijack of a military convoy in Berlin. In the file, Hobbs discovers a recent photo of Dom's former girlfriend Letty Ortiz, who had been presumed dead.