[1][2] She was born in Covina, California, to Mary Ethel (McKillop) and John Richard Stafford, a Western pulp writer.

She wrote two more novels in her career, but her greatest medium was the short story: her works were published in The New Yorker and various literary magazines.

She was seriously injured in an automobile accident with Lowell at the wheel in 1938, a trauma she described in one of her best-known stories, "The Interior Castle," and the disfigurement she suffered as a result was a turning point in her life.

Stafford enjoyed a brief period of domestic happiness with her third husband, A. J. Liebling, a prominent writer for The New Yorker.

By age sixty-three she had almost stopped eating and died of cardiac arrest in White Plains, New York, in 1979.