Born into a Jewish family in New York, Jane Bowles spent her childhood in Woodmere, New York, on Long Island. She developed tuberculous arthritis of the knee as a teenager and her mother took her to Switzerland for treatment, where she attended boarding school. As a teenager she returned to New York, where she gravitated to the intellectual bohemia of Greenwich Village and began to experiment in bisexuality.

She married writer and composer Paul Bowles in 1938.

In 1943 her novel Two Serious Ladies was published. The Bowleses lived in New York until 1947, when Paul moved to Tangier, Morocco; Jane followed him in 1948. While in Morocco, Jane had an intense and complicated lesbian relationship with a Moroccan woman named Cherifa.

Jane Bowles wrote the play In The Summer House, which was performed on Broadway in 1953 to mixed reviews. Tennessee Williams, Truman Capote, and John Ashbery considered her to be one of the finest and most underrated writers of American fiction.

Bowles, who suffered from alcoholism, had a stroke in 1957 at age 40. Her health continued to decline, despite various treatments in England and the United States, until she had to be admitted to a clinic in Málaga, Spain, where she died in 1973.