Mariel Hemingway grew up primarily in Ketchum, Idaho where her father Jack Hemingway had a farm and where her grandfather Ernest Hemingway also spent a great deal of time as a sportsman and writer. Ernest and Margaux Hemingway are both buried in the Ketchum cemetery.

In addition to Ketchum, Mariel spent part of her adolescence growing up in New York and Los Angeles.

Her first role was with her sister Margaux Hemingway 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.

Hemingway's most famous role was probably Tracy in Woody Allen's Manhattan, in which she plays the high school lover of Isaac (Woody Allen). Only 17 at the time, she was nominated for an Oscar for best supporting actress.

Other highlights include her lesbian kiss as a guest star on the television show Roseanne and also has guest starred in an episode called "The Bill". In 1983, she starred as Dorothy Stratten in Star 80, a film about the Playboy star's life and murder. For that role, Hemingway had her breasts enlarged but she had the implants removed in 2001 after one of them ruptured. In the 1982 movie Personal Best she played a bisexual athlete in a movie noted for some explicit (by mainstream standards) lesbian love scenes.

The fact that Mariel Hemingway starred in film or television shows (including a segment on Crossing Jordan on November 18, 2002 in the episode "Scared Straight"), in which she was featured as a lesbian or had lesbian scenes has led to some speculation as to whether she is herself a lesbian. This rumor is not true, though, as Hemingway is chosen for these roles more for her striking appearance as an athletic 6 ft. 1 inch woman with the trademark square jaw of the Hemingways. In fact, Hemingway herself made fun of her lesbian persona in an opening sequence of Saturday Night Live during the September 30, 1995 episode that she hosted.

In reality, Hemingway has been married since December 9, 1984 to writer and director Stephen Crisman and they have two daughters: Dree (born 1987) and Langley (born 1989).