This show features a series of Mighty Mouse cartoons from the Terrytoons library along with Dinky Duck, Gandy Goose, Sourpuss, Heckle & Jeckle and many other characters.

The show ran for 11 years until 1966 when it was replaced by "Mighty Mouse and the Mighty Heroes". By the 1965-66 season, "Mighty Mouse Playhouse" was switched over to color for one more season and it was originally shown in black & white. It was sponsored by Colgate toothpaste.

This was the first regularly scheduled show to air on Saturday mornings on CBS where the network owned the rights to the Terrytoons library.