Various animation styles are used, just like its magazine counterpart. The animation in the Spy vs. Spy skits range from ink scribble style, clean Flash animation, and stop-motion.
This is the second television series that is based on MAD Magazine. The first was the live-action sketch comedy show "MADtv".
Some of the animators that worked on the show, went on to create or developed their own series.
Nicole Parker and Debra Wilson, the former 2 cast members of MadTV, had appeared in the show.