Mimieux appeared in George Pal's film version of H. G. Wells's 1895 novel The Time Machine (1960) starring Rod Taylor, in which she played the character Weena.

However, her first film was Platinum High School (1960), a low budget teen crime drama produced by Albert Zugsmith starring Mickey Rooney for MGM and released two months before The Time Machine.

[6] Her performance in Platinum High School earned her a 1960 Golden Globe Awards nomination for "New Star Of The Year - Actress".

[2] Mimieux guest-starred in an episode of Mr Lucky, then was one of several leads in the highly popular teen comedy-drama Where the Boys Are (1960), along with Dolores Hart, Paula Prentiss, and Connie Francis.

Mimieux had a central role in the romantic drama Light in the Piazza (1962), playing a mentally disabled girl.

Mimieux went to United Artists for Toys in the Attic, based on the play by Lillian Hellman and co-starring Geraldine Page and Dean Martin.

She played a surfer suffering from epilepsy, a performance that was much acclaimed[11] and led to a 1965 Golden Globe nomination for "Best Actress In A Television Series".

[citation needed] Mimieux was in a Western with Max von Sydow for 20th Century Fox, The Reward (1965); the Disney comedy Monkeys, Go Home!

[12] Mimieux did The Desperate Hours (1967) for TV and was reunited with Rod Taylor in the MGM war movie Dark of the Sun (1968).

[13] In 1968, Mimieux was top-billed in the sex comedy Three in the Attic, a hit for AIP starring Christopher Jones,[14] and then appeared in the critically acclaimed 1969 movie The Picasso Summer alongside Albert Finney.

[citation needed] Mimieux had one of the leads in The Most Deadly Game (1970–1971), a short-lived TV series from Aaron Spelling.

[17] Mimieux was an air hostess in MGM's hostage thriller Skyjacked (1972), starring Charlton Heston and James Brolin[18] and was in the Fox science-fiction film The Neptune Factor (1973).

[citation needed] Mimieux played a falsely imprisoned woman pursued by corrupt law enforcement in the crime drama Jackson County Jail (1976) with Tommy Lee Jones and Robert Carradine for New World Pictures, which was a box-office hit.

Mimieux appeared in such horror-oriented TV movies as Snowbeast (1977), Devil Dog: The Hound of Hell (1978), and Disaster on the Coastliner (1979).