The actress would later credit the show as her claim to fame and an incredible learning experience, and call Walt Disney her "second father." She once stated, "I've always found Mr. Disney to be somewhat of a shy person, a kid at heart."

After leaving The Mickey Mouse Club, Annette Funicello remained under contract to Disney and appeared on TV shows such as Zorro (1957) and The Nine Lives of Elfego Baca (1958). She also starred in a number of Disney feature films, including The Shaggy Dog (1959), Babes in Toyland (1961), The Misadventures of Merlin Jones (1964) and The Monkey's Uncle (1965).

In the early 1960s, Funicello starred in a series of beach party films with Frankie Avalon, including Beach Party (1963), Muscle Beach Party (1964), Bikini Beach (1964), Beach Blanket Bingo (1965) and How to Stuff a Wild Bikini (1965). During this time, she also recorded a series of Top 40 pop singles, including "Tall Paul," "First Name Initial," "How Will I Know My Love" and "Pineapple Princess."

In 1987, Funicello again teamed up with Frankie Avalon to co-produce and star as parents of a pair of troublesome teenagers in Paramount's Back to the Beach. Then, in 1989 and 1990, Avalon and Funicello staged a nostalgic concert tour, performing the beach party music and hit singles they made famous in the 1960s.

In 1992, Funicello announced that she had been battling multiple sclerosis, a degenerative neurological disease, since 1987. To assist in fundraising to fight neurological disorders, the actress founded the Annette Funicello Teddy Bear Company, which markets a line of collectible bears. She also developed her own perfume line, Cello by Annette. A portion of the proceeds from these products goes to the Annette Funicello Research Fund for Neurological Disorders, an organization founded by the actress in 1993.

Annette Funicello died on April 8, 2013, at age 70, at Mercy Southwest Hospital in Bakersfield, California. She was survived by second husband Glen Holt, whom she married in 1986, and three children from her earlier marriage to Jack Gilardi (1965-1981). In her later years, Funicello resided in Encino, a small neighborhood in Los Angeles' San Fernando Valley.