Chosen from hundreds of eager young hopefuls to debut on the pioneering Mickey Mouse Club, Funicello proved a talented standout and received the lion's portion of fan mail. As she matured and her womanly attributes blossomed, Disney quietly removed her from the show. Funicello stayed busy though, showing up as a regular on such series as "The Danny Thomas Show" (1957), "Zorro" (1958), and her own shortlived series "Annette" (1958) where she played a country girl who comes to live with relatives in the big city.

Funicello made her feature debut in the Revolutionary war drama "Johnny Tremaine" (1957) but snared her first substantial supporting role in the fantasy "The Shaggy Dog" (1959) about a boy who falls under an ancient spell and turns into a sheepdog. Starting with "Beach Party" (1963) a slew of innocuous beach movies followed, many teaming her with bubble gum idol Frankie Avalon. After appearing in the psychedelic rock'n'roll comedy "Head" (1968), directed by Bob Rafelson and co-written by Jack Nicholson, Funicello didn't make another screen appearance until 1987 in "Back to the Beach", a sleeper hit which reunited her with Avalon. Her last big screen credit was a cameo appearance as herself in the comedy "Troop Beverly Hills" (1989).

In the 1980s and early 90s Funicello popped up regularly on the small screen mostly in Disney related specials and celebrity guest spots. For a number of years she was the spokeswoman for Skippy peanut butter and was regularly featured in their advertising campaign. In 1992, Funicello went public with the news that she had been suffering from multiple sclerosis since 1987. She co-wrote her autobiography, "A Dream Is a Wish Your Heart Makes" in 1994 and played herself in a cameo appearance at the end of the 1995 TV adaptation.