Ben Stiller (Larry Daley), Amy Adams (Amelia Earhart), Owen Wilson (Jedediah Smith), Robin Williams (Teddy Roosevelt), Hank Azaria (Kahmunrah / Der Denker / Abe Lincoln), Christopher Guest (Ivan der Schreckliche), Alain Chabat (Napoleon Bonaparte), Dick van Dyke (Cecil), Steve Coogan (Octavius), Ricky Gervais (Dr. McPhee), Bill Hader (George Armstrong Custer), Jon Bernthal (Al Capone), Patrick Gallagher (Attila), Jake Cherry (Nicky), Rami Malek (Ahkmenrah), Mizuo Peck (Sacajawea), Jay Baruchel (Matrose Joey Motorola), Carla Gugino (Rebecca), Clint Howard (Flight Commander Johnson), George Foreman (er selbst), Mickey Rooney (Gus), Bill Cobbs (Reginald), Kim Raver (Erica Daley), Eugene Levy (Albert Einstein)