Cars takes place in a world populated by anthropomorphic transportation. The film begins with the last race of the Piston Cup championship, which 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, Lightning 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 reckless street racers, causing McQueen to fall out the back of the truck into the road. McQueen wakes in the middle of traffic, and speeds off the highway to find Mack, ending up in the run-down town of Radiator Springs and inadvertently ruining the pavement of its main road.
After being arrested and impounded overnight, guarded by a rusty but friendly tow truck named Mater, McQueen is ordered by the town's judge and doctor, Doc Hudson, to leave town immediately. The local lawyer, Sally Carrera, insists that McQueen be given community service to repave the road, to which Doc begrudingly agrees. McQueen tries to repave it in a single day, but it turns out to be shoddy and McQueen is ordered to repave the road again, which takes several days to complete. During this time, he becomes friends with several of the cars, and learns that Radiator Springs used to be a popular stopover along U.S. Route 66, but with the construction of Interstate 40 bypassing the town, it literally vanished from the map. McQueen also discovers that Doc is really the "Fabulous Hudson Hornet", a three-time Piston Cup winner who was forced out of racing after an accident and quickly forgotten by the sport. McQueen finishes the road, which has invigorated the cars to improve their town, and spends an extra day in town with his new friends, before Mack and the media descend on the town, led by a tip to McQueen's location. McQueen reluctantly leaves with the media to get to California in time for the race, while Sally chastises Doc after discovering that he had tipped off the media to McQueen's whereabouts, not wanting to be discovered himself instead.
At the speedway, McQueen's mind is not fully set on the race, and he soon falls into last place. He is surprised to discover that Doc Hudson, decked out in his old racing colors, has taken over as his crew chief, along with several other friends from Radiator Springs to help in the pit. Inspired and recalling tricks he learned from Doc and his friends, McQueen quickly emerges to lead the race into the final laps. Hicks, refusing to lose, sends Weathers into a dangerous accident. Seeing this and recalling Doc's fate, McQueen stops just short of the finish line, allowing Hicks to win, and drives back to push Weathers over the finish line. The crowd and media condemn Hicks' victory and give praise to McQueen's sportsmanship. Though offered the Dinoco sponsorship deal, McQueen declines, insisting on staying with his current sponsors as an appreciation of their past support. Later, back at Radiator Springs, McQueen returns and announces that he will be setting up his headquarters there, helping to put Radiator Springs back on the map.
- Ash Ketchum, Pikachu, Misty, Togepi, Brock and the Pokemon gang, Simba, Nala, Timon, Pumbaa, Zazu, Kovu, Kiara, Ma, Uncle Max, Rafiki, Littlefoot, Cera, Ducky, Petrie, Spike, Chomper, Ruby, Guido, Grandpa Longneck, Grandma Longneck and the Land Before Time Gang, SpongeBob SquarePants, Patrick Star, Squidward Tentacles, Sandy Cheeks, Eugene Krabs and the gang, Bloom, Stella, Flora, Musa, Tecna, Layla, Stan Marsh, Kyle Broflovski, Eric Cartman, Kenny McCormick, Jean-Bob, Speed, Puffin, Terk, Tantor, Louis, Ray the Firefly, Genie, Iago, Sebastian, Baloo, Bagheera, King Louie, the Vultures, Jiminy Cricket, Mickey Mouse, Donald Duck, Goofy, Kenai, Koda, Rutt and Tuke, Fu Dog, Roger Rabbit, Woody, Buzz Lightyear, Charlie Barkin, Itchy Itchiford, Jack Skellington, Chanticleer, Owen, Izzy, Bowser, Mistress Nine, Bowser Jr., Ranamon, Oogie Boogie, Bob the Tomato, Larry the Cucumber, Junior Asparagus, Jimmy and Jerry Gourd, the Powerpuff Girls (Blossom, Bubbles, and Buttercup), the Rugrats Gang, Carly Shay, Sam Puckett, Alvin, Brittany, Bobby, Cindy, Oliver, Freddie Benson, Spencer Shay, Gibby, the Muppets (Kermit the Frog, Miss Piggy, Fozzie Bear, Gonzo, Rizzo the Rat, Waldorf and Statler, Sam the Eagle, Animal, and the Electric Mayhem), Popeye, Olive Oyl, Popeye's Nephews (Peepeye, Poopeye, Pipeye, and Pupeye), Scrooge McDuck, Huey, Dewey, Louie, Webby, Launchpad McQuack, Chip and Dale, Lilo, Stitch, Pleakey, Jumba, Mario, Luigi, Princess Toadstool, Toad, Yoshi, Donkey Kong, Diddy Kong, Sonic the Hedgehog, Miles "Tails" Prower, Knuckles the Echidna, Amy Rose, Cream the Rabbit, Cheese the Chao, Shadow the Hedgehog, Rouge the Bat, Team Chaotix (Vector the Crocodile, Espio the Chameleon, and Charmy the Bee), Silver the Hedgehog, Blaze the Cat, Spyro the Dragon, Sparx the Dragonfly, Banjo and Kazooie, Barney the Dinosaur, Baby Bop, BJ, Riff, The Griffins (Peter, Lois, Chirs, Meg, Brian, and Stewie), Pocahontas, Meeko, Flit, Princess Aurora, Peter Pan, Tinkerbell, Terrence, Fawn, Rosetta, Silvermist, Iridessa, Vidia, Alice, Hercules, Phlioctetes, Pegasus, Phineas and Ferb, Isabella Garcia-Shapiro, Alex, Marty, Melman, Gloria, The Penguins of Madagscar (Skipper, Kolwalski, Rico, and Private), King Julien, Maurice, Mort, Taran, Princess Eilonwy, Fflewddur Fflam, Gurgi, Jesse Greenwood, Elvis, Randolph Johnson, Nadine, The Goonies (Mikey Walsh, Brand Walsh, Mouth Devereaux, Data Wang, Chunk Cohen, Andy Carmichael, Stef Steinbrenner, and Sloth Fratelli), Aladdin, Princess Jasmine, Abu, Yogi Bear, Boo-Boo Bear, Snagglepuss, Huckleberry Hound, Quick Draw McGraw, Augie Doggie and Doggie Daddy, Wally Gator, Magilla Gorilla, Top Cat, Peter Potamus, Scrooge McDuck, Huey, Dewey and Louie, Webby, Tom, Huckleberry, Becky, Scooby-Doo, Shaggy Rogers, Fred Jones, Daphne Blake, Velma Dinkley, Bugs Bunny, Daffy Duck, Woody Woodpecker, Ttark, Rex, Woog, Elsa, Dweeb, Fievel Mousekewitz, Tiger, Tony Toponi, Tanya Mousekewitz, Yasha Mousekewitz, Papa Mousekewitz, Mama Mousekewitz, Kids World's Adventures Team, Hubie, Marina, Rocko, Makunga, Stan Marsh, Kyle Broflovski, Eric Cartman, Kenny McCormick, Mickey Mouse, Donald Duck, Goofy, Jesse Greenwood, Elvis, Randolph Johnson, Nadine, The Goonies (Mikey Walsh, Brand Walsh, Mouth Devereaux, Data Wang, Chunk Cohen, Andy Carmichael, Stef Steinbrenner, and Sloth Fratelli), Bugs Bunny, Daffy Duck, Taran, Princess Eilonwy, Fflewddur Fflam, Gurgi, Jack Skellington, Scooby-Doo, Shaggy Rogers, Fred Jones, Daphne Blake, Velma Dinkley, The Vultures (Buzzie, Flaps, Dizzy, and Ziggy), Jiminy Cricket, Zazu, Kronk, Rex, Woog, Elsa, Dweeb, Charlie Barkin, Itchy Itchiford, Jean-Bob, Speed, Puffin, Kenai, Koda, Rutt and Tuke, Roger Rabbit, Po the Panda, Shifu, The Furious Five (Tigress, Monkey, Mantis, Crane, and Viper), and the characters will guest star in this film.