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. She sold flowers in San Francisco as a teenage runaway. In a conversation with novelist and short story writer Matthew Sharpe for "BOMB Magazine", Gaitskill said she chose to become a writer at age 18 because she was "indignant about things—it was the typical teenage sense of 'things are wrong in the world and I must say something.'" Gaitskill has also recounted (in her essay "Revelation") becoming a born-again Christian at age 21 but lapsing after six months.