This movie was inspired by an early 1990s McDonald's ad about Pee-Wee Football that ran during the Super Bowl. The day after it aired, Steven Spielberg liked it so much that he called up the ad's creator, James Ferguson, and hired him to write the script.
Devon Sawa was 15 during filming and much taller than his ten-year-old castmates, so he can be seen wearing only socks in some scenes.
Duwayne Dunham was removed as director after shooting more than two-thirds of the film. He fell behind during the football game sequences. Brian Levant was brought in for the last few weeks to finish the football sequences, using Rexford L. Metz as his cinematographer. Dunham was retained to supervise the editing at the same time, however, which he saw through to completion.
Ten years after the film's release, the real-life New York Giants (whom the Little Giants were named after) introduced a solid-red alternate jersey similar to the ones their pee-wee namesakes wore. The red alternates were worn by the Giants from 2004 to 2009.