Her mother taught her to speak French fluently and she was educated at the Lycée Français Charles de Gaulle in London, leading many to believe erroneously that she was born in France. When Bisset was a teenager, her mother was diagnosed with disseminating sclerosis. After her parents divorced, she moved in to help her mother. She had taken ballet lessons as a young child, and now began taking acting lessons, and fashion modelling to pay for them.

In 1967, Bisset was cast in the critically acclaimed movie Two for the Road. Next, she participated in the James Bond spoof Casino Royale (1967), as Miss Goodthighs.

In 1968, Mia Farrow dropped out of a movie named The Detective (1968), and the role went to Bisset. She was cast opposite Steve McQueen in Bullitt in 1968.

In 1973, she appeared in François Truffaut's movie Day for Night, where she earned the respect of European critics and moviegoers as a serious actress. In 1977, Bisset made great strides towards becoming a better known entertainer in America with her movie The Deep (1977), co-starring Robert Shaw, where her appearance swimming underwater wearing only a T-shirt made many to credit her with popularizing the wet T-shirt contest. At the time, Newsweek magazine declared her to be "the most beautiful film actress of all time."

Soon thereafter she played in the movies Rich and Famous (1981) with Candice Bergen, and Under The Volcano with Albert Finney (1984) and earned her a second Golden Globe award nomination. In 1978 she had already earned her first Golden Globe nomination for the comedy Who is Killing the Great Chefs of Europe?.

In 1996, she was nominated for a César Award, France's version of the Oscars, for her role in La cérémonie.

During her career, Bisset has worked with such legendary directors as François Truffaut, John Huston, George Cukor and Roman Polański, among others. Several of her movies are French or Italian productions.

Bisset has also appeared in many made-for-TV movies, especially during the last 10 years, some of which have been quite successful. One of her later TV movies, released in 2003, was America's Prince: The John F. Kennedy Jr. Story, in which she portrayed Jacqueline Kennedy.

Bisset has never married, but her heterosexuality has never been in question.

Bisset is the godmother to actress Angelina Jolie. She starred opposite Jolie in the film Mr. and Mrs. Smith (2005). The scenes never made the final cut.