Factual error: The Times Square Jumbotron has a ticker-tape message beneath it. Some of the letters have sections missing, presumably to represent broken bulbs. If this is the case, the missing parts would not scroll with the message, as it's only the constant switching on and off of the bulbs that gives the impression of movement.
Continuity mistake: In the scene where they're in the air close to the end of the movie, when Margo tries to jump to Gru's plane, Vector grabs her and points the squid launcher at Gru, then the moon hits Vector, knocking him and Margo off his ship. When Vector climbs back up to his ship, the moon's gone. It couldn't have rolled away because Vector's ship didn't move in that short time.
Continuity mistake: At the very end of the movie the 3 girls are performing on stage. Agnes is wearing white tights, but after the platform raises them all above the house she no longer has tights, just bare legs.
Continuity mistake: Justin, the boy with the toy aircraft running away from his mother, towards the pyramid in the beginning of the movie, has the toy in his left hand while going up the ramp, while falling and as he begins traveling up through the air but when the angle of view changes it is in his right hand until he lands on his father.
Continuity mistake: When Gru gets shot with all those guns at the end of his attempts to get in Vector's house before he first sees the girls, his goggles are at the top of his head. After he gets shot, the dust is not over his eyes, indicating that his goggles were over his eyes, shielding them from the dust.
Continuity mistake: In the scene where Gru goes to get Agnes, Margo, and Edith from Vector from his "lair" (after giving him the moon) he puts his face against the camera and it displays Gru as taking up the full screen. When he then punches the camera it shows only a small portion of the screen is taken up.
Continuity mistake: In the very first shot of inside the orphanage, the tape mark on the floor is at least 3 feet away from the desk. The three girls stand behind it and 2 shots later we can see they are standing about an inch away from the desk. Then when Miss Hattie stands up, the tape is now a foot away from the table.