Continuity mistake: In the opening sequence Sacajawea is placed in a crate of tan, straw-like packing material. When Larry visits the museum a few hours later, Sacajawea emerges from a crate full of white packing "peanuts" (styrofoam pellets).
Continuity mistake: When Jedediah is in the hour glass, he is in the lower chamber, and the area between is too small for him to go through. When the minions are returning to the portal, in a close up he is obviously in the top chamber, only to return to the bottom when Octavius breaks him free.
Continuity mistake: In the scene where Larry and Amelia escape into the VJ Day photograph, Larry is seen speaking to a sailor in dress blues. Throughout the exchange the rating badge on the sailor's arm changes from crossed keys, the insignia for storekeeper to lightning bolts, the insignia for radioman several times.
Factual error: Larry and Amelia Earhart both fly the Wright Flyer using a stick control. It was actually controlled using a mechanism attached to the pilot's hips whereby he could turn the aircraft by shifting his body from side to side.
Factual error: On the shoulder of the Tuskegee Airmen, their 'American Flag' patch is seen having 50 stars. At the time of WWII, the US flag only had 48, and 48 would have been the number they'd wear.
Continuity mistake: When Custer is explaining how they will yell "Attack!" before attacking and Sacajawea questions the veracity of this plan, she is first in front of the caveman, etc. (with her back to the door of the box-crate) and then with no one behind her (with her back to the side of the box-crate).
Continuity mistake: The way crates are placed differs enormously between the moment before and after the dinosaur throws Ben Stiller flying. Watch the crates on the back: First they are spread apart, perpendicular to the animal, but when Stiller lands they're parallel and close together to hide the safety crash mat in between.