In addition to directing sounds for animated shorts as aurally complicated as Mickey's Trailer, he developed many original inventions and contraptions to achieve expressive sounds for characters like Evinrude the dragonfly from The Rescuers, the bees in Winnie the Pooh and the Honey Tree, and Spike the bee who gets to the best of Donald Duck in the 1950s cartoon shorts.
By 1947, Walt Disney was getting too busy and too hoarse from smoking to continue voicing Mickey Mouse, so he was replaced by MacDonald, after the film Fun and Fancy Free. (A common misconception is that MacDonald had voiced additional dialogue shared with Disney in that film.) MacDonald voiced the mouse on a regular basis until 1953 (Disney had briefly taken over for The Mickey Mouse Club) and a recurring one until his retirment in 1977, when he was replaced by young Disney sound effects man Wayne Allwine for The New Mickey Mouse Club; Allwine's first theatrical role for Mickey was in Mickey's Christmas Carol.
MacDonald was also the voice of Goofy at one time, where he provided his voice in the 1960s Disney record album Donald Duck and His Friends.
MacDonald also provided the voice for Jaq and Gus in Cinderella, the Dormouse and Flamingos in Alice in Wonderland, Humphrey the Bear, and the Wolf in The Sword in the Stone. He also appeared in Toby Tyler as a circus band drummer, but was uncredited.
MacDonald had also played drums for the Firehouse Five Plus Two jazz band on and off from its inception until it disbanded in the early 1970s.
His chimney lamp growls would later be reused for the 1987 Tri-Star live action feature, The Monster Squad, as the stock growling for the Wolfman.