Parts of the filming were done in front of a green screen, and everything the characters did not interact with or touch was animated in post-production. Parts of the film, which were shot in live-action, were animated during post-production using a technique similar to the rotoscoping used in Linklater's Waking Life (2001) and A Scanner Darkly (2006).
Jack Black, who voices older Stan, has a personal connection to NASA and the space program. His mother, Judith Love Cohen, helped develop the Abort-Guidance System which ultimately helped get Apollo 13 back to Earth, while she was pregnant with Jack.
Richard Linklater was planning to create the film in live action but instead decided to go with an animation style influenced by Saturday morning cartoons because of the playful nature of animation. This proved controversial as the Academy of Motion Picture Arts and Sciences denied the movie eligibility for the Animated Feature category for the 2023 Academy Awards in July 2022. After an appeal from the filmmakers and the outcry of much of the industry, the decision was reverted in early January 2023.
Prior to the launch of Apollo 10½, Stan is seen reading the July, 1969 edition of Mad Magazine. (Although Apollo 10½ is said to have launched weeks before Apollo 11 on July 16, this would not be an anachronism, as Mad Magazine cover dates were generally 2-3 months later than their actual publication, so the July edition would have been on newsstands as early as May.)
The two NASA officials who run Stan's flight training are named Bostick and Kranz after NASA engineers Jerry Bostick and Gene Kranz.