Warren was born in New York City, New York, the daughter of Carol (née Verblow), a singer, and William Warren, a real estate agent. Her family, whose surname is originally "Warrenoff", was of Russian Jewish descent. Her 1967 marriage to producer Jon Peters ended in divorce in 1977. They have one son, Christopher Peters (born 1968, now an actor). She married Ronald Taft in 2000.

The 5-foot-8 inch Warren began her career as a ballet dancer, training at the School of American Ballet. She entered the Actors Studio at the age of 17 — reputedly the youngest applicant ever to be accepted. Her Broadway debut came in 1963 in the musical, 110 in the Shade. She won the Theatre World Award for her performance in the 1965 flop musical Drat! The Cat!. In 1973, she portrayed Scarlett O'Hara in the Los Angeles production of the musical Scarlett; however the play was poorly reviewed and didn't continue to Broadway as planned.

Having failed to obtain the role of Liesl in the film version of The Sound of Music, Warren's first major television success was in the title role of Rodgers and Hammerstein's television special, Cinderella, in 1965. She later played the part of Dana Lambert, the leading female on the Mission: Impossible team during the 1970-1971 television season. According to The Complete Mission: Impossible Dossier by Patrick White, she was considered too inexperienced for the part and left after only one year. Despite her departure, throughout the 1970s, Warren became a leading lady of TV movies, TV series and TV miniseries. She even hosted her own episode of The Muppet Show and made an occasional feature film. Warren also played Lois Lane in the 1975 TV special It's a Bird...It's a Plane...It's Superman, adapted from the Broadway musical of the same name. Warren went on to screen-test for the role of Lois Lane in the 1978 Superman film, a role that was ultimately won by Margot Kidder (footage of Warren's screen-test has been included as a supplemental feature on VHS and DVD releases of the film).

For her portrayal of a dim-witted gangster's moll in the 1982 musical-comedy Victor Victoria, Warren was nominated for an Academy Award for Best Actress in a Supporting Role. Warren is also a five-time Golden Globes nominee and won for the 1977 miniseries Harold Robbins' 79 Park Avenue. She was Emmy-nominated for the TV movie Family of Spies (1991).

In 1975, Warren played a disturbed mental patient opposite Peter Falk and George Hamilton in the Columbo episode A Deadly State of Mind. In the comedy film version of the popular board game Clue (1985), she starred as one of the prime murder suspects, Miss Scarlet. In 1986, Lesley was prominently featured in Bob Seger's popular music video for his hit song "American Storm". In 1989, she appeared in Aerosmith video "Janie's Got a Gun" where she played Janie's mother.

Warren had recurring roles on Will & Grace as Will Truman's father's mistress, and on Desperate Housewives as Susan Mayer's mother. Other television roles have included Lily Lebowski's mother on Crossing Jordan and Kip Stedman's mother in Less than Perfect.

Warren plays the role of Mary Shannon's mother in the USA Network original television series, In Plain Sight.

Linda Cristal (1969) · Peggy Lipton (1970) · Patricia Neal (1971) · Gail Fisher (1972) · Lee Remick (1973) · Angie Dickinson (1974) · Lee Remick (1975) · Susan Blakely (1976) · Lesley Ann Warren (1977) · Rosemary Harris (1978) · Natalie Wood (1979) · Yoko Shimada (1980) · Linda Evans/Barbara Bel Geddes (1981) · Joan Collins (1982) · Jane Wyman (1983) · Angela Lansbury (1984) · Sharon Gless (1985) · Angela Lansbury (1986) · Susan Dey (1987) · Jill Eikenberry (1988) · Angela Lansbury (1989)

Complete List · (1969-1989) · (1990–present)