Lowell was born to Commander Robert Traill Spence Lowell III and Charlotte Winslow in Boston, Massachusetts. The Lowells were a Boston Brahmin family that included poets Amy Lowell and James Russell Lowell; clergymen Charles Russell Lowell, Sr. and Robert Traill Spence Lowell; Civil War general and war hero Charles Russell Lowell III (about whom Lowell wrote his poem "Charles Russell Lowell: 1835-1864"); and the Federal Judge John Lowell.
His mother was a descendant of Ben William Samuel Johnson, a signer of the United States Constitution; Jonathan Edwards, the Calvinist theologian (about whom Lowell wrote the poems "Mr. Edwards and the Spider," "Jonathan Edwards in Western Massachusetts," "After the Surprising Conversions," and "The Worst Sinner"); Anne Hutchinson, the Puritan preacher and healer; Robert Livingston (who was also an ancestor on Lowell's paternal side); Thomas Dudley, the second governor of Massachusetts; and Mayflower passengers James Chilton and his daughter Mary Chilton. Lowell's parents share a common descent from Philip Livingston, the son of Robert Livingston, which means they were sixth cousins.
As well as a family history steeped in Protestantism, Lowell had notable Jewish ancestors on both sides of his family, which he discusses in Part II ("91 Revere Street") of Life Studies. On his father's side, Lowell was the great-great-grandson of Maj. Mordecai Myers (father of Theodorus Bailey Myers, Lowell's great-granduncle), a soldier in the War of 1812 and later mayor of Kinderhook and Schenectady; and on his mother's side, he is descended from the Mordecai family of Raleigh, North Carolina, who were prominent in state affairs.
As a youth, Lowell had a penchant for violence and bullying other children. Describing himself as an 8½-year-old in the prose piece "91 Revere Street," Lowell wrote that he was "thick-witted, narcissistic, thuggish". As a teenager, Lowell's peers gave him the nickname "Cal" after both the villainous Shakespeare character Caliban and the tyrannical Roman emperor Caligula, and the nickname stuck with him throughout his life. Lowell would later reference the nickname in his poem "Caligula," first published in his book For the Union Dead and later republished in a revised sonnet version for his book Notebook 1967–1968.
Lowell received his high school education at St. Mark's School, a prominent prep-school in Southborough, Massachusetts. There he met and was influenced by the poet Richard Eberhart, who taught at the school, and as a high school student, Lowell decided that he wanted to become a poet. At St. Mark's, he became lifelong friends with Frank Parker, an artist who later created the prints that Lowell used on the covers of most of his books.
Lowell attended Harvard College for two years. While he was a freshman at Harvard, he visited Robert Frost in Cambridge and asked for feedback on a long poem he had written on the Crusades; Frost suggested that Lowell needed to work on his compression. In an interview, Lowell recalled, "I had a huge blank verse epic on the First Crusade and took it to him all in my undecipherable pencil-writing, and he read a little of it, and said, 'It goes on rather a bit, doesn't it?' And then he read me the opening of Keats's 'Hyperion,' the first version, and I thought all of that was sublime."
After two years at Harvard, Lowell was unhappy, and his psychiatrist, Merrill Moore, who was also a poet, suggested that Lowell take a leave of absence from Harvard to get away from his parents and to study with Moore's friend, the poet-professor Allen Tate who was then living in Nashville and teaching at Vanderbilt. Lowell traveled to Nashville with Moore who took Lowell to Tate's house. Lowell asked Tate if he could live with him and his wife, and Tate joked that if Lowell wanted to, Lowell could pitch a tent on Tate's lawn; then Lowell went to Sears, Roebuck to purchase a tent that he set up on Tate's lawn and lived in for two months. Lowell called the act "a terrible piece of youthful callousness".
After spending time with the Tates in Nashville (and attending some classes taught by John Crowe Ransom at Vanderbilt), Lowell decided to leave Harvard. When Tate and John Crowe Ransom left Vanderbilt for Kenyon College in Ohio, Lowell followed them and resumed his studies there, majoring in Classics. He settled into the so-called "writer's house" (a dorm that received its nickname after it had accrued a number of ambitious young writers) with fellow students Peter Taylor, Robie Macauley and Randall Jarrell.
Partly in rebellion against his parents, Lowell converted from Episcopalianism to Catholicism; however, by the end of the forties, he would leave the Catholic Church. After Lowell graduated from Kenyon in 1940 with a degree in Classics, he worked on a Master's degree in English literature at Louisiana State University and taught introductory courses in English for one year before the U.S. entered World War II.
Lowell was a conscientious objector during World War II and served several months at the federal prison in Danbury, Connecticut. He explained his decision not to serve in World War II in a letter addressed to President Franklin Roosevelt on September 7, 1943, stating, "Dear Mr President: I very much regret that I must refuse the opportunity you offer me in your communication of August 6, 1943 for service in the Armed Force." He explained that after the bombing at Pearl Harbor, he was prepared to fight in the war until he read about the American terms of unconditional surrender that he feared would lead to the "permanent destruction of Germany and Japan." Before Lowell was transferred to the prison in Connecticut, he was held in a prison in New York City that he later wrote about in the poem "Memories of West Street and Lepke" from his book Life Studies.
Lowell's letter to the president was his first major political act of protest, but it would not be his last. During the mid to late 1960s, Lowell actively opposed the Vietnam War. In response to American air raids in Vietnam in 1965, Lowell rejected an invitation to the White House Festival of the Arts from President Lyndon Johnson in a letter that he subsequently published in The New York Times, stating, "We are in danger of imperceptibly becoming an explosive and suddenly chauvinistic nation, and may even be drifting on our way to the last nuclear ruin."  Ian Hamilton notes that "throughout , [Lowell] was in demand as a speaker and petition signer [against the war]. He was vehemently opposed to the war, but equivocal about being identified too closely with the 'peace movement': there were many views he did not share with the more fiery of the 'peaceniks' and it was not in his nature to join movements that he had no wish to lead."  However, Lowell did participate in the October 1967 March on the Pentagon in Washington, DC against the war and was one of the featured speakers at the event. Norman Mailer, who was also a featured speaker at the rally, introduced Lowell to the crowd of protesters. Mailer described the peace march and his impression of Lowell that day in the early sections of his "non-fiction novel" The Armies of the Night. Lowell was also a signer of the anti-war manifesto "A Call to Resist Illegitimate Authority" circulated by members of the radical intellectual collective RESIST.
In 1968, Lowell publicly supported the Minnesota Senator Eugene McCarthy in his campaign for the Democratic nomination for president in a three-way primary against Robert F. Kennedy and Hubert Humphrey. Lowell spoke at numerous fundraisers for McCarthy in New York that year, but "[his] heart went out of the race" after Robert Kennedy's assassination.
From 1950 to 1953, Lowell taught in the well-reputed Iowa Writers' Workshop at the University of Iowa, together with Paul Engle and Robie Macauley. Later, Donald James Winslow hired Lowell to teach at Boston University, where his students included the poets Sylvia Plath and Anne Sexton. Over the years, he taught at a number of other universities including the University of Cincinnati, Yale University, Harvard University, and the New School for Social Research. Numerous poets, critics and scholars, including Kathleen Spivack, James Atlas, Helen Vendler, and Dudley Young have written essays about Lowell's teaching style and/or about his influence over their lives. In 2012, Spivack also published a book, With Robert Lowell and His Circle, about her experience studying with Lowell at Boston University in 1959. From 1963 to 1970, Lowell commuted from his home in New York City to Boston in order to teach classes at Harvard.
The scholar Helen Vendler attended one of Lowell's poetry courses and wrote that one of the best aspects of Lowell's informal style was that he talked about poets in class as though "the poets [being studied] were friends or acquaintances". Hamilton quoted students who stated that Lowell "taught 'almost by indirection,' 'he turned every poet into a version of himself,' [and] 'he told stories [about the poets' lives] as if they were the latest news.'"
In March 2005, the Academy of American Poets named Life Studies one of their Groundbreaking Books of the 20th century, stating that it had "a profound impact", particularly over the confessional poetry movement that the book helped launch. The editors of Contemporary Literary Criticism wrote that the book "exerted a profound influence on subsequent American poets, including other first generation confessionalists such as Sylvia Plath and Anne Sexton." In a 1962 interview, Sylvia Plath stated that Life Studies had influenced the poetry she was writing at that time (and which her husband, Ted Hughes, would publish posthumously as Ariel a few years later): "I've been very excited by what I feel is the new breakthrough that came with, say, Robert Lowell's Life Studies, this intense breakthrough into very serious, very personal, emotional experience which I feel has been partly taboo. Robert Lowell's poems about his experience in a mental hospital, for example, interested me very much." In an essay published in 1985, the poet Stanley Kunitz wrote that Life Studies was "perhaps the most influential book of modern verse since T. S. Eliot's The Waste Land."
During the 1960s, Lowell was the most public, well-known American poet; in June 1967, he appeared on the cover of Time as part of a cover story in which he was praised as "the best American poet of his generation." Although the article gave a general overview of modern American poetry (mentioning Lowell's contemporaries like John Berryman and Elizabeth Bishop), Lowell's life, career, and place in the American literary canon remained the article's focus.
Lowell married the novelist and short-story writer Jean Stafford in 1940. Before their marriage, in 1938, Lowell and Stafford got into a serious car accident, in which Lowell was at the wheel, that left Stafford permanently scarred, while Lowell walked away unscathed. The accident crushed her nose and one of her cheekbones and required her to undergo multiple reconstructive surgeries. The couple had a tumultuous marriage that ended in 1948. The poet Anthony Hecht characterized the marriage as "a tormented and tormenting one." Then, shortly thereafter, in 1949 Lowell married the writer Elizabeth Hardwick with whom he had a daughter, Harriet, in 1957. After Hardwick's death in 2007, The New York Times would characterize the marriage as "restless and emotionally harrowing," reflecting the very public portrait of their marriage and divorce as Lowell captured it in his books For Lizzie and Harriet and The Dolphin. After 23 years of marriage to Elizabeth Hardwick, in 1970, Lowell left her for Caroline Blackwood. Blackwood and Lowell were married in 1972 in England where they decided to settle and where they raised their son, Sheridan. Lowell also became the stepfather to Blackwood's young daughter, Ivana, for whom he would write the sonnet "Ivana," published in his book The Dolphin.
Lowell had a close friendship with the poet Elizabeth Bishop that lasted from 1947 until Lowell's death in 1977. Both writers relied upon one another for critiques of their poetry (which is in evidence in their voluminous correspondence, published in the book Words in Air: the Complete Correspondence between Elizabeth Bishop and Robert Lowell in 2008) and thereby influenced one another's work. Bishop's influence over Lowell can be seen at work in at least two of Lowell's poems: "The Scream" (inspired by Bishop's short story "In the Village") and "Skunk Hour" (inspired by Bishop's poem "The Armadillo"), and the scholar Thomas Travisano notes, more broadly, that "Lowell's Life Studies and For the Union Dead, his most enduringly popular books, were written under Bishop's direct influence."
Lowell also maintained a close friendship with Jarrell from their 1937 meeting at Kenyon College until Jarrell's 1965 death. Lowell openly acknowledged Jarrell's influence over his writing and frequently sought out Jarrell's input regarding his poems before he published them. In a letter to Jarrell from 1957, Lowell wrote, "I suppose we shouldn't swap too many compliments, but I am heavily in your debt."
Lowell suffered from manic depression and was hospitalized many times throughout his adult life for this mental illness. On multiple occasions, Lowell was admitted to the famous psychiatric hospital, McLean Hospital, in Belmont, Massachusetts, and one of his poems, "Waking in the Blue" references his stay there. Although Lowell's manic depression was often a great burden (for himself and his family), the subject of that mental illness led to some of his most important poetry, particularly as it manifested itself in his book Life Studies. When he was fifty, Lowell began taking lithium to treat his mental illness. Saskia Hamilton, the editor of Lowell's Letters, notes, "Lithium treatment relieved him from suffering the idea that he was morally and emotionally responsible for the fact that he relapsed. However, it did not entirely prevent relapses ... And he was troubled and anxious about the impact of his relapses on his family and friends until the end of his life."
Lowell died in 1977, having suffered a heart attack in a cab in New York City on his way to see his ex-wife, Elizabeth Hardwick. He was buried in Stark Cemetery, Dunbarton, New Hampshire.