She was known for her performances in the films I Wanna Hold Your Hand (1978), Bachelor Party (1984), and Back to the Future (1985), as well as the television sitcoms Bosom Buddies (1980–1982) and Private Benjamin (1982–1983).

[2] Sperber began her screen career at age 19 when she was cast in the small role of Kuchinsky in Matthew Robbins' 1978 teen movie Corvette Summer, alongside Mark Hamill and Annie Potts.

[3] She played the title role in the television movie Dinky Hocker, an ABC Afterschool Special which dealt with a teenager's attempts to hide her feelings by eating.

Zemeckis, who also worked on 1941, brought her back to the big screen in 1980 with a role in his comedy Used Cars, but it was on television that year that Sperber began to receive more serious attention.

She was cast in the role of Amy Cassidy — a character who was funny, romantic, and exuberant — in the series Bosom Buddies, starring Tom Hanks and Peter Scolari.

Her last work was voicing a character on the animated TV series American Dad (episode titled "Roger 'n' Me") that aired in 2006, after her death.