The basic premise is that Mickey Mouse and his friends run a dinner theater club called the "House of Mouse" in downtown , which shows Disney cartoons as part of its floor shows. Located at a corner of an intersection on Toontown's Main Street, the club is considered a very popular destination by the local populace. Some episodes have specific themes, with cartoons to fit that episode's theme. The theme is usually not beneficial to at least one character, usually Donald.
Many characters from Disney animated films (such as Aladdin, Pinocchio, Peter Pan, The Little Mermaid, Hercules, and many more) have appeared on House of Mouse, mostly as patrons and guest star performers. The show is notable for including many relatively obscure and otherwise rarely-used Disney characters, often with speaking parts. Notably, Li'l Bad Wolf and April, May and June Duck, who had appeared very often in Disney comic books but never before in an animated cartoon, finally made their animated debuts on House of Mouse. The show also featured some cameos by characters created for other television cartoons and theme park attractions, but these appearances were few and far between.Each episode explores the comical mishaps of Mickey and his associates running the club, which are used as wraparounds for Disney cartoons (some of which are classic theatrical cartoons from the 1930s, 1940s and 1950s, but most of which are reruns from Mickey Mouse Works).