She was married to an actor 30 years older, John Derek, from 1974 until his death in 1998. They met during filming of a movie, and subsequently, John filed for divorce from his wife, actress Linda Evans.

She appeared in Orca: the Killer Whale (1977), in which her character's (Annie) leg was bitten off when the whale attacked her home on a pier.

Derek co-starred in the 1979 Blake Edwards film 10, in which she vied with a foul-mouthed Julie Andrews for Dudley Moore's attention. Her appearance in the popular sex farce shot her to instant stardom and status as a sex symbol.

The plotline of 10 involves a woman who seems better-than-perfect to the protagonist (Moore), until he actually gets to know her and realizes she cannot live up to his expectations. Subsequent films have not been well-received by either the public or critics. The 1981 film Tarzan, the Ape Man was a disappointment. The producers of the film were actually sued by the Edgar Rice Burroughs Estate over the name of the film, since it focused more on how many ways to disrobe Jane (Derek's role), than on Tarzan himself.

The sex-drenched Bolero (1984) essentially ended any possibility of a substantial film career. Critics and viewers looked carefully at the scenes of actual intercourse to spot a body double for Derek, and found none.

Her subsequent role in her husband's production Ghosts Can't Do It firmly cemented her reputation as a sex object.

Bolero and Tarzan, the Ape Man earned her the dubious honor of four Golden Raspberry Awards, as well as a nomination in 2000 as the "Worst Actress of the Century". Her most respectable showing was as Jamie Kennedy's mom and Ryan O'Neal's wife in Malibu's Most Wanted (2003).

She is a conservative Republican who supported George H.W. Bush and campaigned for his son, George W. Bush in 2000 and 2004, and she appeared at both Republican conventions. Derek also appeared at public events with conservative Republican and supporter of traditional values, Congressman David Dreier of Southern California .

Currently, Derek lives with her boyfriend, actor John Corbett, in the Santa Ynez Valley, California. She published her autobiography on February 5th, 2002 entitled "Riding Lessons, Everything I learned in life I learned from horses."