A small, delicate-looking, perky actress, Thompson studied dance as a child, and was dancing professionally by age 14; she won scholarships to the Pennsylvania Ballet, American Ballet, and the San Francisco Ballet. However, she felt she was too short to become a prima ballerina and gave up dance in favor of acting. After moving to New York she appeared in some 20 Burger King TV commercials, then debuted onscreen in Jaws 3-D (1983). Shortly thereafter she got her first important role, opposite Tom Cruise in the hit All the Right Moves (1983). She is best known for her multiple roles in the three Back to the Future movies; aside from those highly successful movies, she has not gone on to appear in any hit productions. She also appeared in the TV movies Nightbreaker (1989), Montana (1990), and the PBS playhouse co-production The Wizard of Loneliness (1988).
- Danced with the Pennsylvania Ballet Company, the American Ballet Theatre and the San Francisco Ballet.
- Made a series of commercials for Burger King before her film debut in Jaws 3-D (1983).
- Turned down the role of Amanda in Some Kind of Wonderful (1987), but reconsidered after urging from the director, who became her husband.
- Won a 1999 TV GUIDE Award for her work in Caroline in the City.
- Appeared on the 2006 Fox reality series Celebrity Duets, and performed two duets with Belinda Carlisle.
- Also in 2006, directed the cable film Jane Doe: The Harder They Fall and also directed a 2008 cable film, Jane Doe: Eye of the Beholder. (She starred in both films.)
- Appears in the 2011 Clint Eastwood-directed drama, J. Edgar, starring Leonardo DiCaprio. She called working with DiCaprio "one of the most amazing days of my life" and joked that the star may have been annoyed that day when she mentioned her husband had once made a macaroni-and-cheese ad with him.