The series originally aired 125 episodes from May 5, 2006, to November 6, 2016, on the Disney Channel's preschool block, Playhouse Disney (later known as Disney Junior), making it the longest-running original series to air on the block. The show features two original songs performed by American alternative rock band They Might Be Giants, including the opening theme song, in which a variant of a Mickey Mouse Club chant ("Meeska Mooska Mickey Mouse!") is used to summon the Clubhouse. On August 18, 2023, a revival was revealed to be in production, under the working title "Mickey Mouse Clubhouse+"
Mickey, Minnie, Donald, Daisy, Goofy, and Pluto interact with the viewer to stimulate problem solving during a self contained story. Mickey invites the viewers to join him at the Mousekedoer, a giant Mickey-head-shaped computer whose main function is to distribute the day's tools to Mickey. The show features two original songs performed by American alternative rock band They Might Be Giants, including the opening theme song.