Mary Gaitskill was born in Lexington, Kentucky. She has lived in New York City, Toronto, San Francisco, Marin County and Pennsylvania, as well as attending the University of Michigan, where she earned her B.A. in 1981 and won a Hopwood Award.
Gaitskill has taught at UC Berkeley, the University of Houston, New York University, The New School, Brown University, in the MFA program at Temple University and Syracuse University. She was the Writer-In-Residence at Hobart and William Smith Colleges. As of 2020, Gaitskill is a visiting professor of literature at Claremont McKenna College.
The story collection Bad Behavior, was published in 1988. The first four stories are written in the third person point of view from the perspectives of male characters. The remaining five stories are written from the perspectives of female characters. Several of the stories have themes of sexuality, romance, love, sex work, sadomasochism, drug addiction, being a writer in New York City, and living in New York City. A Romantic Weekend and Secretary both explore themes of BDSM and psychological aspects of dominance and submission in sexual relationships. The story Connection is about a female friendship.
The film Secretary (2002) is based on the short story of the same name in Bad Behavior, although the two have little in common. She characterized the film as "the Pretty Woman version, heavy on the charm and a little too nice."
The novel The Mare, published in 2015, is written from the perspectives of several different characters. The primary characters are named Ginger and Velvet (short for Velveteen). Ginger is a middle-aged woman who meets Velvet, a young adolescent, through The Fresh Air Fund.
Gaitskill's honors include a Guggenheim Fellowship in 2002 and a PEN/Faulkner Award nomination for Because They Wanted To in 1998. Veronica (2005) was a National Book Award nominee, as well as a National Book Critics Circle finalist for that year. The book is centered on the narrator, a former fashion model and her friend Veronica who contracts AIDS.