Carson McCullers was born Lula Carson Smith on 19 February 1917 in Columbus, Georgia. Her father was a jeweller and watchmaker of French descent. 

From the age of 5 she learned to play the piano. When she was 17, she announced her intention to leave home to study at the Juillard School of Music in New York. Her family sold two heirlooms to pay for her passage by steamship and tuition fees, but on arrival in New York the money was misplaced. Unwilling to ask her family for more money, Carson took a series of menial jobs, studying writing in the evenings first at Columbia University and then NYU. In 1936 her first short story, Wunderkind, was published in Story Magazine. 

In 1937 she married an ex-soldier called Reeves McCullers. They moved to Charlotte, North Carolina, and it was here she started work on a book originally titled The Mute. It was published as The Heart Is A Lonely Hunter in 1940, and in the same year the couple separated. Carson moved back to New York, where she joined the eccentric household of "February House". George Davies, then editor of Harper's Bazaar, bought a large house in Brooklyn and persuaded McCullers, along with WH Auden, to join him there. Other artists and writers joined the commune (named by Anais Nin after the number of residents with February birthdays). Other members of this bohemian family included Benjamin Britten, Peter Pears, Gypsy Rose Lee, Golo Mann, Salvador Dali and Leonard Bernstein

After World War II, McCullers lived primarily in Paris, near to her close friends Truman Capote and Tennessee Williams. She reunited with Reeves McCullers in 1945. In 1953 he tried to convince her to join him in a suicide pact; she left him. He killed himself in Paris. 

Carson McCullers suffered from chronic illness and alcoholism. She had strokes from a young age, and by 31 was paralysed down one side. She died in 1967 from a brain hemorrhage. She was 50 years old.

Throughout her life, McCullers was somewhat sexually ambiguous. Despite her marriage and relationships with other men, there has been much speculation about the nature of her sexuality. She declared herself an introvert and once stated "I was born a man". She had a number of unrequited romantic infatuations with beautiful and powerful women. One incident involved McCullers throwing herself at the feet of Katherine Anne Porter at the Yaddo artistic community. Porter merely stepped over her on her way to dinner.