After defeating Owen Shaw and his crew and securing amnesty for their past crimes, Dominic "Dom" Toretto, Brian O'Conner, and the rest of their team have returned to the United States to live normal lives again. Brian begins to accustom himself to life as a father, while Dom tries to help Letty Ortiz regain her memories. Meanwhile, Owen's older brother, Deckard Shaw, breaks into the secure hospital the comatose Owen is being held in and swears vengeance against Dom, before breaking into Luke Hobbs' DSS office to extract profiles of Dom's crew. After revealing his identity, Shaw engages Hobbs in a fight, and escapes when he detonates a bomb that severely injures Hobbs. Dom later learns from his sister Mia that she is pregnant again and convinces her to tell Brian. However, a bomb, disguised in a package sent from Tokyo, explodes and destroys the Toretto house just seconds after Han, a member of their team, is killed by Shaw in Tokyo. Dom later visits Hobbs in a hospital, where he learns that Shaw is a rogue special forces assassin seeking to avenge his brother. Dom then travels to Tokyo to claim Han's body, where he meets and races Sean Boswell, a friend of Han's, who gives him personal items found at Han's crash site.
Following their successful Rio heist, Dominic "Dom" Toretto and his professional criminal crew have fled around the world: Dom lives with Elena; his sister Mia lives with Brian O'Conner and their son, Jack; Gisele and Han live in Hong Kong; and Roman and Tej live in luxury.
When Dominic "Dom" Toretto is being transported to Lompoc Prison by bus, his sister Mia Toretto and friend Brian O'Conner lead an assault on the bus, causing it to crash and freeing Dom. While the authorities search for them, the trio escapes to Rio de Janeiro. Awaiting Dom's arrival, Mia and Brian join their friend Vince 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 Administration (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, is only interested in stealing one car, a Ford GT40. Dom has Mia steal the car herself before 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, 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.
In a world populated by anthropomorphic vehicles, the last race of the Piston Cup championship ends in a three-way tie between retiring veteran Strip "The King" Weathers, infamous runner-up Chick Hicks, and rookie Lightning McQueen. The tiebreaker race is scheduled for one week later at the (fictional) Los Angeles International Speedway in California. Lightning is desperate to win the race, since it would allow him to leave the unglamorous sponsorship of Rust-Eze, a rust treatment for old cars, and allow him to take The King's place as the sponsored car of the lucrative Dinoco team. Eager to start practice in California as soon as possible, he pushes his big rig, Mack, to travel all night long. While McQueen is sleeping, the exhausted Mack drifts off and is startled by a gang of four reckless street racers, causing McQueen to fall out the back of the trailer and into the road. McQueen wakes in the middle of traffic and speeds off the highway to find Mack, only to end up in the run-down desert town of Radiator Springs, and inadvertently ruining the pavement of its main road.
Five years after leaving Los Angeles, Dominic Toretto and his new crew, consisting of his girlfriend Letty, Tego Leo, Rico Santos, Cara Mirtha, and Han Seoul-Oh, are hijacking fuel tankers in the Dominican Republic. Dominic begins to suspect that the police are hot on their trail, after Han informs him that one of his garages have been raided, forcing the crew to disband and go their separate ways. Realizing that he must move, he packs his things in the middle of the night and leaves Letty behind in order to protect her from harm.
In a suburban San Fernando Valley garden in Los Angeles, Theo, a.k.a. Turbo, is a snail who dreams of being the greatest racer in the world, just like his hero, 5-time Indianapolis 500 champ, Guy Gagné. His obsession with speed and all things fast has made him an outcast in the slow and cautious snail community, and a constant embarrassment to his older brother, Chet. Turbo desperately wishes he could escape the slow-paced life he's living, but his one chance to live proves a near fatal disaster when he tries to recover a prize tomato and needs to be rescued by Chet.
After allowing fugitive Dominic Toretto (Vin Diesel) to evade arrest, former LAPD officer Brian O'Conner (Paul Walker) finds himself on the run from the FBI and leaves Los Angeles to start a new life. He travels across the U.S. in a red Mitsubishi GTO, entering various drag races and winning large amounts of money. The FBI issues a country-wide manhunt against Brian and one day, the police locate him and repossess his car, forcing him to leave on foot. A girl (Minka Kelly) picks him up after he hitches a ride, and she drops him off at the local car lot, where he buys a 1999 Nissan Skyline GT-R R34 with the money he won. After winning several more races, he decides to settle in Miami.
On docks outside Los Angeles, a semi-truck is loaded with electronics, but a corrupted dock worker informs an unknown person about the truck shipment. During the night, while the truck drives on the interstate, it is approached by three heavily modified black Honda Civics with green underglow. The occupants of the Civics immobilize the truck driver, hijack the truck and escape, passing through a roadblock and stealing thousands of dollars worth of shipment.
Tobey Marshall is a former race car driver who owns a Mount Kisco, New York garage, where he and his friends tune performance cars. Struggling to make ends meet, he and his crew participate in street races after hours. One day, Dino Brewster, Tobey's former rival, arrives at his garage in a Mercedes-Benz SLR McLaren with an offer to complete the build of a rare Ford Shelby Mustang worked on by the late Carroll Shelby. Dino wants Tobey and his crew to complete the project in exchange for 25% of the car's estimated selling price of $2 million. Despite objections from the crew, Tobey agrees to the deal.
College student Nick O'Bannon watches a race at McKinley Speedway for a study break with his girlfriend Lori Milligan, and their friends Janet Cunningham and Hunt Wynorski. While watching the race, Nick has a premonition that a race car crash will send debris into the stands, causing the stadium to collapse, and killing numerous people. When Nick panics, a fight breaks out, and several people leave before Nick's vision becomes a reality including Lori, Janet, Hunt; security guard George Lanter; mechanic Andy Kewzer; mother Samantha Lane; tow truck driver Carter Daniels; and Andy's girlfriend Nadia Monroy. Nadia gets angry and yells at them when she is suddenly obliterated by a stray tire that flies out of the stadium.
Ricky Bobby (Will Ferrell) is a NASCAR driver who wants to go fast. While he was working on the pit crew of Dennit Racing driver Terry Cheveaux (Adam McKay), Ricky replaces him and ends up finishing in third place, despite starting mid-race in last place. Ricky quickly soars to the top of NASCAR by achieving his fame and fortune at Dennit Racing and meeting his future wife, Carly (Leslie Bibb). Ricky eventually persuades Dennit to field an additional car and arranges to have his best friend, Cal Naughton, Jr. (John C. Reilly), on his team. While he and Cal are on top of the racing world, Ricky challenges his flamboyant French Formula One archrival, Jean Girard (Sacha Barone Cohen), who outperforms him on the track and becomes Dennit Racing's next top driver. Desperate to regain his dominance, Ricky pushes himself too hard during the race at Charlotte Motor Speedway and ends up going airborne, barrel-rolling several times.
In Arizona, 17-year-old high school student Sean Boswell (Lucas Black) and Clay (Zachery Ty Bryan) race their cars to win Clay's girlfriend Cindy (Nikki Griffin). When Sean cuts through a structure and catches up to Clay, Clay hits Sean's car repeatedly until a high speed turn which causes the pair to both crash; Clay's wealthy family helps him escape punishment, but Sean's numerous past racing activities causes his mother to send him to live with his father in Tokyo, who is stationed there for the U.S. Navy.
Cole Trickle is a young racer from Glendale, California, with years of experience in open-wheel racing winning championships in the Indycar Series. His goal was to win the Indianapolis 500 but realises that "You can't win at Indy without a great car and my name isn't Andretti or Unser". He is recruited by Chevrolet dealership tycoon Tim Daland to race for his team in the NASCAR Winston Cup Series. Daland also convinces former crew chief and car builder Harry Hogge to come out of retirement and lead Cole's pit crew. After Trickle sets a fast time in a private test at Charlotte, Hogge builds him a new Chevrolet Lumina to drive in the Winston Cup, though the season has already started.
In early September, 1962, recent high school graduates and longtime friends, Curt Henderson and Steve Bolander, meet John Milner and Terry "The Toad" Fields at the local Mel's Drive-In parking lot. Despite receiving a $2,000 scholarship from the local Moose lodge, Curt is undecided if he wants to leave the next morning with Steve to go to the northeastern United States to begin college. Steve lets Toad borrow his 1958 Chevrolet Impala for the evening and while he's away at college. Steve's girlfriend, Laurie, who also is Curt's sister, is unsure of Steve's leaving, to which he suggests - to Laurie's surprise - they see other people while he is away to "strengthen" their relationship. She is not happy with his proposal.