Hemingway was born in Mill Valley, California, the daughter of Byra Louise (née Whittlesey) and Jack Hemingway, a writer.
Her paternal grandfather was writer Ernest Hemingway and her sister was Margaux Hemingway; she never met her grandfather, as he died several months before she was born.
She was named after the Cuban port of Mariel - a village that her father and grandfather visited regularly as sportsmen to fish. Her middle name was after her paternal grandmother, Elizabeth Hadley (née Richardson).
Hemingway grew up primarily in Ketchum, Idaho, where her father lived, and where her paternal grandfather also spent a great deal of time as a sportsman and writer. Mariel also spent part of her adolescence growing up in New York and Los Angeles.
Hemingway's first role was with her sister Margaux in the 1976 film Lipstick. The movie was not considered especially good, but Mariel did receive notice for the quality of her acting, and she was nominated as "Best Newcomer" for the Golden Globes Award that year.
In the 1982 movie Personal Best, she played a bisexual athlete in a movie noted for some explicit (by mainstream standards) lesbian love scenes.
In 1983, she starred as Dorothy Stratten in Star 80, a film about the Playboy model's life and murder. For that role, Hemingway had her breasts enlarged. Her implants were later removed in 2001 after one of them ruptured.
Hemingway was featured in newly discovered deleted footage, which was shown in a very rough edit with unfinished visual effects, from Superman IV: The Quest For Peace and was released on DVD in November 2006 as a Deluxe Edition and as part of The Ultimate Superman Collection.
Hemingway has played a lesbian in several film or television shows, including Personal Best, an infamous episode of the sitcom Roseanne in which she kissed Roseanne Barr on the lips, and an episode of Crossing Jordan, but the actress is not gay.
Hemingway has said she formed a "big connection with the gay and lesbian community" after Personal Best and enjoys taking roles in "cutting-edge" productions.
Hemingway made fun of her reputation for lesbian roles during a 1995 appearance on Saturday Night Live when she kissed new female cast members during her opening monologue as host.
In television, she played the lead role of Sydney Guilford in the legal drama series Civil Wars, from 1991-1993. In 1995 she played another leading role in TV, this time in the first season of the drama series Central Park West. She left the show after the first season.
She has made guest appearances in a number of television shows, including Tales From the Crypt in 1991 (in which she became the first actress to appear naked in the show), Roseanne, Becker, Crossing Jordan and Law & Order.
She also acted in the 1987 mini-series Amerika.
Hemingway has been married since December 9, 1984 to writer and director Stephen Crisman, and they have two daughters: Dree (b. 1987) and Langley (b. 1989).
She is the author of the 2006 self-help book "Mariel Hemingway's Healthy Living from the Inside Out: Every Woman's Guide To Real Beauty, Renewed Energy, and a Radiant Life".