Not unlike a number of poets, writers, and other creative individuals, Conrad Aiken's personal and professional life was informed by an early tragedy. Born in Savannah, Georgia, he was traumatized when he discovered the bodies of his parents. His father, a brilliant but unstable physician, had killed Aiken's mother and then himself. Aiken was only a young child, eleven years old.

Later, in his "autobiographical narrative," he lamented that finding his parents dead was so traumatic that he "found himself possessed of them forever." Like his father, he sometimes suffered from depression, and when he reached the age his father had been when he committed suicide, his depression deepened.

After his parents' death, Aiken was taken to Massachusetts and raised by a great-great-aunt. He received a private education, and entered Harvard upon his high school graduation. There, he met fellow student, T.S. Eliot. The two together edited the Advocate. Aiken stated that Eliot's work helped to inform his own writing. Other students attending Harvard at the same time included Walter Lippman, Van Wyck Brooks, and E.E. Cummings.

Aiken graduated in 1912 and soon married Jessie McDonald, a graduate student from Canada. For a time he worked as a newspaper reporter, but thanks to a small income likely derived from his parent's and aunt's estates, he was able to devote himself to writing full-time. He claimed that his greatest influences were the work of Freud, Havelock Ellis, William James, Edgar Allan Poe, and the French Symbolists. Freud acknowledged Aiken's talent and claimed that his Great Circle was a masterpiece of analytical introspection. Aiken's first poetry collection, Earth Triumphant was published in 1914 and established him as a poet. He also worked as a contributing editor to Dial, which allowed him to meet and form a friendship with Ezra Pound.

Following this period, he began to make a series of trans-Atlantic journeys. In 1921 he and his family settled in Rye, Sussex, England. It was about that time that his marriage began to disintegrate, and the couple divorced in 1929. In 1927-28 Aiken served as a tutor at Harvard. He remarried in 1930, to Clarissa M. Lorenz, a musician and journalist. He was also awarded a Pulitzer Prize in 1930, for his collection Selected Poems. He continued to travel between the East coast of the United States and England, and in 1932 attempted suicide. He and Clarissa divorced, and he married the artist Mary Hoover in 1937. The couple finally settled in Massachusetts, where, in 1950 he was asked by the Library of Congress to serve as a consultant in poetry.

As he grew older, he desired to return to scenes familiar from childhood. In 1962 he began to winter in a Savannah house adjacent to the one in which he had spent his childhood. He eventually lived there year-round, and died in Savannah in the summer of 1973.