Her parents, a psychiatrist father, Julian Janowitz, and literature professor mother, Phyllis Janowitz, divorced when she was ten. She grew up with her mother in Massachusetts.

She graduated from Barnard College with a B.A. in 1977, and from Hollins College with a M.A. in 1979.

She studied at the Columbia University School of the Arts and started writing about life in New York City, where she had settled down.She socialized with Andy Warhol and became well-known in New York's literary and social circles.Her 1986 collection of short stories, Slaves of New York brought her wider fame. Slaves of New York was adapted into a 1989 film directed by James Ivory and starring Bernadette Peters. Janowitz wrote the screenplay and also appeared, playing Peters' friend.

Janowitz has published seven novels, one collection of stories and one work of non-fiction.She lives in Brooklyn with her husband, Tim Hunt, and their adopted daughter.