- Ben Stiller Larry Daley
- Carla Gugino Rebecca
- Robin Williams Theodore Roosevelt
- Dick Van Dyke Cecil Fredricks
- Jake Cherry Nick
- Ricky Gervais Dr. McPhee
- Mickey Rooney Gus
- Paul Rudd Don
- Bill Cobbs Reginald
- Kim Raver Erica Daley
- Patrick Gallagher Atila, rey de los hunos
- Rami Malek Ahkmenrah
- Mizuo Peck Sacajawea
- Anne Meara Debbie
- Brad Garrett Easter Island Head (voz)
- Pierfrancesco Favino Christopher Columbus