Bill Hader as Flint Lockwood, a young, unsuccessful but determined inventor of the food replicator machine FLDSMDFR.
Max Neuwirth as young Flint.
Anna Faris as Samantha 'Sam' Sparks: a weather intern from New York City and later Flint's love interest.
Neil Patrick Harris as Steve, Flint's pet vervet monkey who can communicate through a thought translator Flint invented
James Caan as Timothy 'Tim' Lockwood: Flint's taciturn but caring technophobic fisherman father.
Bruce Campbell as Mayor Shelbourne: the corrupt, greedy and selfish mayor of Swallow Falls. Andy Samberg as 'Baby' Brent McHale: the arrogant and dim-witted mascot of Swallow Falls' sardine cannery and Flint's former rival.
Mr. T as Officer Earl Devereaux: the town's athletic police officer and Cal's father.
Bobb'e J. Thompson as Calvin 'Cal' Devereaux: Earl's young son.
Benjamin Bratt as Manny: Sam's deadpan Guatemalan cameraman and former doctor, pilot, and comedian.
Al Roker as Patrick Patrickson: the anchorman of the weather station.
Lauren Graham as Fran Lockwood: Flint's late mother who had always believed in her son.
Will Forte as Joe Towne: a bearded redneck citizen who appears on numerous occasions throughout the film.
Angela V. Shelton as Regina Devereaux: Earl's wife and Cal's mother.