She is best known for her role as Lorraine Baines-McFly in the Back to the Future film trilogy (1985–1990), Beverly Switzler in Howard the Duck (1986), and Amanda Jones in Some Kind of Wonderful (1987).

[citation needed] At 20, Thompson was dancing with American Ballet Theatre's Studio Company, then known as ABT II.

[citation needed] Mikhail Baryshnikov, who was the artistic director at the time, told her, "You're a lovely dancer, but you're too stocky.

[6] In 1982, Thompson played Cecily "Sissy" Loper in the interactive live-action video game MysteryDisc: Murder, Anyone?.

[7] Thompson's most famous role is that of Lorraine Baines McFly in the Back to the Future trilogy, with the first film released in 1985.

For the latter film, she sang several songs on the soundtrack in character, as musician Beverly Switzler, who was the lead vocalist for a band called Cherry Bomb.

Rounding out film appearances in the late 1980s, Thompson starred in Some Kind of Wonderful, Casual Sex?, and The Wizard of Loneliness.

Thompson found moderate critical and popular success as the star of the NBC sitcom Caroline in the City from 1995 to 1999.

In 2005, Thompson began a series of made-for-TV films for the Hallmark Channel, Jane Doe, in which she played Cathy Davis, an ex-secret agent turned housewife, who helps the government solve mysteries.

[12] Her film credits include Exit Speed, Spy School, Splinterheads, and Adventures of a Teenage Dragon Slayer.

[16] On April 27, 2017, Thompson was cast in the film Little Women, the seventh adaptation of Louisa May Alcott's novel of the same name, written and directed by first-time director Clare Niederpruem.

Thompson portrayed Margaret "Marmee" March, the mother who helps her daughters navigate the struggles and heartbreaks of adolescence and adulthood.

[17] She directed "Family Day", episode 5 of season 2 of the Syfy series Resident Alien, first aired in February 2022.