Robert Traill Spence Lowell IV was born to an old and prosperous New England family. Born in Boston, Massachusetts, his father, also Robert Lowell, was a United States Naval officer. His mother, Charlotte Winslow Lowell, also had deep roots in New England.

Lowell was educated privately in Boston, and later at St. Mark's preparatory school. From his childhood he was interested in words and literature. By the time he was at prep school he had decided upon a writing career. Following his graduation from St. Mark's, he enrolled at Harvard. He was a multi-generational legacy student, as a number of the men in his family had attended Harvard. However, he remained there for only two years. His departure was prompted by poet Allen Tate, who was a member and practitioner of the New Criticism movement in literature.

Lowell spent the summer following his Harvard sophomore year camped out in Tate's back yard, reading and writing poetry. At the end of the summer he decided not to return to Harvard, and instead transferred to Kenyon College, located in Ohio. Kenyon was the alma mater of Allen Tate, and his mentor, John Crowe Ransom, was still on the faculty. Lowell graduated summa cum laude in Classics two years later. He then enrolled as a graduate student at Louisiana State University, studying under Cleanth Brooks and Robert Penn Warren.

Before journeying south, he married Jean Stafford, who wrote short stories and novels. While Lowell enthusiastically embraced the idea of military enlistment when World War II began, he was rejected due to his poor eyesight. Two years later, the Army came calling, anyway, and attempted to draft Lowell. By this time he had become a conscientious objector, and ultimately served several months in jail for refusing to fight. During his jail time he continued to write, and soon after published his first book, Land of Unlikeness. He then revised the book and reissued it as Lord Weary's Castle, which was greeted with critical approval and led to a Pulitzer Prize for Poetry in 1947.

He was earlier named Consultant of Poetry to the Library of Congress, in 1943. In 1948, Lowell and his wife divorced and in 1949 he married Elizabeth Hardwick, who was a writer from Kentucky and had a way with the often tricky waters of the New York literary scene. Lowell's second book was the recipient of great criticism, and so he and Hardwick left the United States to live in Europe for a time. During this period Lowell suffered from several mental breakdowns. He may well have been bi-polar, and his manic-depression plagued him the rest of his life. He was sometimes hospitalized for his condition, particularly when he learned of his mother's death.

Despite his personal struggles, Lowell continued to write, to publish and win awards. He began to take an interest in American history, and such themes are prevalent in his later work. The interest in history led to political activism. He befriended Robert Kennedy, Jacqueline Kennedy, and Senator Eugene McCarthy. In 1974, his book, The Dolphin, won a Pulitzer Prize.

Following his second divorce, he married Caroline Blackwood. The couple relocated to England, but it was Hardwick he was traveling back to New York to see when he died of a heart attack in 1977.