• Jordan Fry and Daniel Hansen as Lewis, a 12-year-old orphaned boy genius who struggles to be adopted. •
Tom Selleck as Cornelius Robinson, Franny's husband, Wilbur's father, and Lewis's older self. •
Wesley Singerman as Wilbur Robinson, the 13-year-old son of Franny and Cornelius Robinson, who is a time-traveler. •
Stephen Anderson as: • Bowler Hat Guy, an evil man with a personal vendetta against Lewis. • Matthew Josten as Michael "Goob" Yagoobian, the Bowler Hat Guy's younger self and Lewis' roommate. • Bud Robinson, an eccentric inventor, Cornelius' adoptive father, Fritz and Joe's older brother, and Wilbur's grandfather. • Cousin Tallulah, Fritz and Petunia Robinson's fashionable daughter and Laszlo's sister. •
Harland Williams as Carl, the Robinson family's robot. •
Nicole Sullivan as Franny Robinson, Cornelius's wife, Wilbur's mother, and Gaston and Art's sister. She trains her frogs to sing and controls the family when Cornelius is not around. •
Michaela Jill Murphy as young Franny •
Angela Bassett as Mildred Duffy, the head of the Sixth Street Orphanage. •
Adam West as Art, a pizza delivery man with a
superhero persona. He is Gaston and Franny's brother and Wilbur's uncle. •
Laurie Metcalf as Lucille Krunklehorn-Robinson, a scientist at InventCo. Labs. She is Lewis' adoptive mother, Bud's wife, and Wilbur's grandmother. •
Ethan Sandler as: • Doris, a bowler hat designed by Cornelius Robinson to be a helping hat but expanded beyond its intelligence and now seeks revenge. • Fritz Robinson, Petunia Robinson's husband, Bud and Joe Robinson's brother, and Laszlo and Tallulah Robinson's father. • Aunt Petunia, a hand puppet who is Fritz Robinson's wife and Laszlo and Tallulah Robinson's mother. • Uncle Spike and Uncle Dimitri, twins who sit in potted plants in front of the Robinson household. It is unknown who they are related to. • Cousin Laszlo, Fritz and Petunia Robinson's son, and Tallulah's brother. • The unnamed CEO of InventCo •
Don Hall as: • Gaston, a
stunt performer who is Franny and Art's brother and Wilbur's uncle. • Gym Coach •
Tom Kenny as Mr. Willerstein, Lewis' teacher. • Kelly Hoover as Aunt Billie, Joe Robinson's wife, who likes trains. • Tracey Miller-Zarneke as Lizzy, a student from Lewis' school who presents her fire ants at the science fair. • Joe Mateo as Tiny, a
Tyrannosaurus brought to the future by the Bowler Hat Guy, who later becomes the Robinson family's pet dinosaur. • Aurian Redson as Frankie the Frog, the lead singer of Franny's musical band of frogs. •
Jamie Cullum as the singing voice of Frankie the Frog •
Paul Butcher as Stanley Pukowski, a student from Lewis' school who presents a volcano at the science fair. • Dara McGarry as: • InventCo Receptionist • Mrs. Harrington • John H. H. Ford as Mr. Harrington •
Nathan Greno as Lefty, a one-eyed purple octopus-like creature and the Robinson family's butler. •
Joe Whyte as a reporter who interviews Lewis. In addition, Joe Robinson is Wilbur's obese uncle, Billie's husband, and Bud and Fritz's brother, who rides in an easy chair; an uncredited actor provides his whimpers. Also in the Robinson family is their dog, Buster, who wears glasses. ==Production==