Dusty Crophopper is a crop duster plane who works at a cornfield and practices aerobatic maneuvers in his spare time, dreaming of becoming a racer. His dreams are scorned by his boss, Leadbottom, and his forklift/mechanic friend, Dottie. However, he is supported by his fuel truck friend, Chug. Dusty and Chug train for qualifiers for the upcoming Wings Across the Globe race. On the night before the qualifiers, Dusty asks an elderly navy war plane named Skipper Riley to teach him how to fly well, but Skipper declines. Dusty qualifies for the race on a legal technicality (fifth place qualifier Fonzarelli was disqualified for usage of an illegal fuel intake).
Skipper decides to mentor Dusty, and discovers Dusty has a fear of heights. With training complete, Dusty travels to New York City to start the race. There, he befriends a Mexican race plane named El Chupacabra, who falls in love with a French-Canadian racer named Rochelle, who shows no interest in him. Three-time winner Ripslinger rudely dismisses Dusty. Dusty falls in love with an Indian racer plane named Ishani, who becomes supportive of him. During the first leg of the race from New York to Iceland, Dusty's refusal to fly high causes him to finish in last place.
During the second leg of the race to Germany, Dusty shows good sportsmanship by saving another racer, Bulldog, from crashing, winning Bulldog's respect but finishing last again.
After the third leg of the race to Agra in India, Ishani invites Dusty to fly around the Taj Mahal and advises him to fly low through the Himalayas by following some railroad tracks. After flying through a tunnel (and narrowly missing a train), Dusty is in first place at Upper Mustang in Nepal, but he is upset to discover that Ishani deliberately gave him bad advice (implied to be under orders from Ripslinger) in exchange for a new propeller, and he shuns her. As the race continues towards Shanghai, Dusty maintains his lead, and helps El Chupacabra woo Rochelle with a romantic song.
In the sixth leg of the race across the Pacific, Ripslinger, refusing to lose the rally, has his henchmen Ned and Zed clip off Dusty's navigation antenna. Lost and low on fuel, Dusty comes across the USS Flysenhower, which allows him to land and refuel. On the carrier, Dusty discovers that Skipper only flew one war mission, which contradicts his reputation.
Continuing the race, Dusty crashes into the ocean but is rescued. Severely damaged, he is flown to Mexico. Skipper confesses that his one mission leading a squadron of new fighters turned tragic, and Skipper was the only survivor, but couldn't bring himself to fly again. Dusty considers dropping out of the race but is encouraged to continue by his fellow competitors, who donate parts to repair the damage he sustained.
Racing back to New York, Ripslinger plots to finish off Dusty, but he is thwarted by Skipper. Dusty conquers his fear of heights when he rides a jetstream. Nearing the finish line, Ripslinger slows for the cameras, which allows Dusty to pass him and win, and Ripslinger crashes into portable toilets. Dusty is congratulated by his friends, and Skipper thanks him for giving him the confidence to fly again. Skipper rejoins the navy, flying one last time with Dusty.