The animated series was co-produced by Scholastic starting in early 1991, based on the original book series by Joanna Cole and Bruce Degen, with the idea developed by former Scholastic vice president Craig Walker.

The National Science Foundation was the first organization to fund a pilot animatic that helped shape the series' development, with the Carnegie Corporation of New York and the U.S. Department of Energy joining as funders afterward.

Lily Tomlin signed on to voice Ms. Frizzle in early 1993, while Malcolm-Jamal Warner agreed to play the recurring role of The Producer around the same time.

The show featured an unusually starry guest cast for a children's series, including Dolly Parton, Ed Asner, Carol Channing, Rita Moreno, Malcolm McDowell, Tyne Daly, Eartha Kitt, and Alex Trebek in various one-off roles.

The theme song, 'Ride on the Magic School Bus,' was written by Peter Lurye and performed by legendary rock musician Little Richard.

The Magic School Bus was the first fully animated series ever aired on PBS, and by the end of its run it was among the network's highest-rated shows for school-age children.

A 2011 Nintendo DS game, The Magic School Bus: Oceans, was released ten years after the previous game in the franchise and remains the only Magic School Bus game ever released on a Nintendo platform.

The franchise was revived by Netflix and Scholastic Media, first announced in 2014 as The Magic School Bus 360° before being renamed The Magic School Bus Rides Again, featuring Lily Tomlin reprising Ms. Frizzle alongside Kate McKinnon as her younger sister, with a theme song performed by Lin-Manuel Miranda.