Jennifer Jason Leigh was born Jennifer Lee Morrow in Los Angeles, California, the daughter of writer Barbara Turner and actor Vic Morrow. Her father was of Russian Jewish descent and her mother was of Austrian Jewish ancestry. She is the sister of Carrie Ann Morrow and half-sister of actress Mina Badie.

Jennifer's parents divorced when she was two. Jennifer worked in her first film at the age of nine, in a nonspeaking role for the film Death of a Stranger (1973). At 14 she attended summer acting workshops given by Lee Strasberg and later landed a role in the Disney TV movie The Young Runaways (1978). She received her Screen Actors Guild membership for an episode of the TV series Baretta (1975) when she was 16. Jennifer performed in several TV movies and dropped out of Pacific Palisades High School six weeks short of graduation for her major role in the film Eyes of a Stranger (1981). Her first major success came as the female lead in Fast Times at Ridgemont High (1982).

Jennifer was married to writer/director Noah Baumbach from 2005 to 2013, and the two have a son.