In Savannah, Aiken's father became a respected physician and eye surgeon, while his mother was the daughter of a prominent Massachusetts Unitarian minister.

[3] After his parents' deaths, he was raised by his great-aunt and uncle in Cambridge, Massachusetts, attending Middlesex School, then Harvard University.

This helped Aiken shape his poetry more freely while his recognition of a God grounded his more visually rich explorations into the universe.

[3] Though Aiken was reluctant to speak of his early trauma and ensuing psychological problems, he acknowledged that his writings were strongly influenced by his studies of Sigmund Freud, Carl G. Jung, Otto Rank, Ferenczi, Adler, and other depth psychologists.

He was married three times: firstly to Jessie McDonald (1912–1929); secondly to Clarissa Lorenz (1930–1937) (author of a biography, Lorelei Two); and thirdly to the painter Mary Hoover (1937–1973).

That year Burra painted his gouache "John Deth", inspired by Aiken's poem of that name and originally intended to illustrate a projected edition that was never realized.

In the following year the couple visited Malcolm Lowry in Cuernavaca, Mexico, where Aiken divorced Clarissa and married Mary.

The Aikens settled in Brewster, Massachusetts, on Cape Cod, where he and his wife Mary later ran a summer program for writers and painters named after their antique farmhouse, "Forty-One Doors".

[12] The Aikens lived primarily at their farmhouse in West Brewster and wintered in Savannah in a home adjacent to his early childhood house.

[13] Aiken died on 17 August 1973, aged 84, and was buried in Bonaventure Cemetery in Savannah, Georgia, on the banks of the Wilmington River.

According to local legend, Aiken wished to have his tombstone fashioned in the shape of a bench as an invitation to visitors to stop and enjoy a martini at his grave.

[15] Aiken was the first Georgia-born author to win a Pulitzer Prize, and was named Georgia's Poet Laureate in 1973.

[17] In 2009, the Library of America selected Aiken's 1931 story "Mr. Arcularis" for inclusion in its two-century retrospective of American fantastic tales.