- Craig T. Nelson as Bob Parr/Mr. Incredible, the patriarch of the Parr family, possessing super-strength.
- Holly Hunter as Helen Parr/Elastigirl, Bob's wife, able to stretch her body like rubber.
- Spencer Fox as Dashiell Robert "Dash" Parr/The Dash, the Parrs' 4th-grader son, gifted with super-speed.
- Sarah Vowell as Violet Parr, the Parrs' middle-schooler daughter, who possesses the ability to turn invisible and create a force shield around herself or other people.
- Eli Fucile and Maeve Andrews as Jack-Jack Parr, Bob and Helen's infant son, who initially shows no powers but near the end of the film reveals himself to have an enormous range of abilities including shape-shifting, teleporting, laser vision, self-immolation, flight, etc.
- Jason Lee as Buddy Pine/Syndrome, who has no super powers of his own but uses advanced technology to give himself equivalent abilities.
- Samuel L. Jackson as Lucius Best/Frozone, Bob's close friend, who has the ability to form ice from himself and from the humidity in the air.
- Elizabeth Peña as Mirage, Syndrome's agent who lures Supers to the island.
- Brad Bird as Edna Mode, fashion designer for the Supers.
- Bud Luckey as Rick Dicker, the government agent overseeing the Relocation Program.
- Wallace Shawn as Gilbert Huph, Bob's boss at his white-collar job.
- John Ratzenberger as The Underminer, a new villain who appears at the end of the film.
- Dominique Louis as Bomb Voyage, a villain from the past who uses Buddy's interference in Mr. Incredible's heroism to escape.
- Bret Parker as Kari McKeen, the babysitter.