The daughter of a prosperous Kansas City dentist, Harlow moved to Los Angeles with her mother after her parents' separation. Educated at the Hollywood School for Girls and at Ferry Hall Seminary in Highland Park, Illinois, she abruptly quit school when she eloped at age 16. Her marriage broke up in 1928 when, against her husband's wishes, she embarked upon an acting career. While briefly under contract to comedy producer Hal Roach (Roach, Hal), she attracted considerable attention with a small but memorable role in the Laurel and Hardy two-reeler Double Whoopee (1929), in which her legendary legs were revealed for the first time on screen. After making her talking-picture debut in Clara Bow's The Saturday Night Kid (1929), she caught the eye of industrialist and erstwhile film producer Howard Hughes (Hughes, Howard), who hired her to replace Swedish actress Greta Nissen in the revised talkie version of his silent aviation epic Hell's Angels (1930). Though her performance was uneven, she created a mild sensation with the now-classic line “Would you be shocked if I put on something more comfortable?”

Harlow's professional success was in marked contrast to her private life, which was plagued by disappointment and tragedy. Her second marriage, to MGM executive Paul Bern, was terminated by his apparent suicide in 1932. She married a third time, to cinematographer Harold Rosson, but they were divorced within a year. She was about to marry longtime fiancé and frequent costar William Powell, when she became seriously ill. Diagnosed with uremic poisoning, she died at age 26. Her final film, Saratoga (1937), was released posthumously, with bit player Mary Dees standing in for Harlow in several scenes.