William Carlos Williams was born on September 17, 1883, in Rutherford, New Jersey, the same town where he would die nearly eighty years later. His father, William George Williams, was a British-born merchant who, since childhood, had lived in the Caribbean. His mother, Rachel Elena Hoheb, was from Puerto Rico and had studied painting in Paris. The couple moved to Rutherford shortly after their marriage in Brooklyn, New York. Williams, and his younger brother Edgar, attended elementary school in Rutherford, and in 1898 studied at Château de Lancy, a boarding school near Geneva, while their father was in Buenos Aires on a year-long business trip. In the fall of 1899, Williams started high school at Horace Mann in Manhattan, commuting roughly an hour and a half each way from Rutherford to Morningside Heights.

Williams entered the University of Pennsylvania in 1902, as a student in its medical program. At Penn, Williams formed friendships with fellow student Ezra Pound, as well as painter Charles Demuth, who was studying art at Drexel, and H. D. (Hilda Doolittle), a student at Bryn Mawr. These friendships encouraged Williams to explore his aesthetic ambitions and would remain important throughout his life. Pound, in particular, was a chief foil in Williams' development of his vision of American literature. The two writers shared a life-long, if at times contentious, friendship. In his prologue to (1920), Williams would call Pound "the best enemy United States verse has" because, from Williams' perspective, Pound favored that which mimicked the European over that which was American. It became one of Williams' aesthetic missions to create a distinctively American literature–one which drew on American diction, rhythms, forms, and themes, and which was rooted in the particularities of the local.

Following medical school, Williams interned first at the French Hospital and then at Nursery and Child's Hospital in New York, resigning from the latter on principle rather than sign his name to a hospital report containing figures he could not verify. Williams next studied pediatrics in Leipzig. While in Europe, he visited Pound in London and had a brief taste of the literary scene there. Upon returning to Rutherford, Williams established a medical practice in his hometown and, in December of 1912, married Florence Herman. The couple would have two sons, William and Paul.

In 1909, Williams privately printed a volume of his poems in Rutherford; and then in 1913 he succeeded in publishing with Pound's publisher, London-based Elkin Matthews. While many of his literary peers led bohemian lives in Greenwich Village and Paris, Williams juggled his writing with his life in suburban Rutherford and his busy medical career. In his 1951 , Williams wrote that early on he had made the decision that he would "not 'die for art,' but live for it, grimly! And work, work, work (like Pop), beat the game and be free (like Mom, poor soul!) to write, write as I alone should write."

During the late 1910s, Williams would sometimes meet with a group of writers associated with the little magazine at the house of Alfred Kreymborg in Grantwood, New Jersey. He also made commutes into Greenwich Village to visit with writers like Marianne Moore, Marsden Hartley, Kay Boyle, Wallace Stevens, Mina Loy, and Lola Ridge. In 1920, Williams founded the little magazine with writer Robert McAlmon. He also continued to contribute his own writing to various little magazines and during the early 1920s published (1920), (1921), (1923), (1923), and (1925). Much of this last book was written during a sabbatical year, half of which he spent in Europe. Though Williams did make several extended trips to Europe during the 1920s, he chose not to become an expatriate like so his many of his peers. In 1926, he won the award for his poem a precursor to the long-poem of the same name he would publish in five books beginning in 1946.

In 1931, Williams contributed to the Objectivist issue of magazine, with fellow poets Louis Zukofsky, Charles Reznikoff, George Oppen and others. In the 1930s, Williams continued to publish extensively, including two volumes of collected poems and the short story collections (1932) and (1938). Williams' fiction often depicted the local middle- and working-class figures that he encountered in his medical practice.

During the late 1930s, Williams, who always had a difficult time finding a stable publisher, began publishing with the fledgling press New Directions. Its founder, James Laughlin, brought out Williams' 1937 novel, , and served as his principal publisher throughout the late 1930s and 1940s. In 1950, though, Williams was wooed by a former New Directions editor, David McDowell, into a lucrative contract to publish several volumes of prose with the more commercial Random House.

Living at a remove from modernism's literary colonies, Williams was a diligent correspondent throughout his life. In addition to carrying on extensive correspondences with his literary peers, he responded to almost anyone who wrote to him, including many young writers. During the 1940s, he met and began a correspondence with aspiring writer Marcia Nardi, whose desperate and sometimes accusatory letters he incorporated into his epic poem .

For much of his life, Williams felt neglected in comparison to some of his better-known contemporaries; however, in the 1950s he began to achieve some the renown he desired. Members of a younger generation of writers, like Allen Ginsberg and Denise Levertov, sought him out as a literary mentor. Such recognition, however, was offset by several medical and personal setbacks. In 1948, Williams suffered a heart attack, and throughout the 1950s he suffered a series of strokes and wrestled with bouts of depression. In the midst of this, Williams also commenced his periodic interviews with scholar John C. Thirlwall, who hoped to write a biography of the poet. Williams' own had caused tensions with some of his old literary compatriots, including a major rift with his one-time friend Robert McAlmon.

Williams also experienced disappointment when his nomination to the post of Consultant in Poetry at the Library of Congress was sidetracked by McCarthy-era questions about his politics and personal associations, including his friendship with Pound. Ill-health and frustration led him to surrender the appointment. He did, however, that same year receive the validation of sharing the 1953 Bollingen Prize with Archibald MacLeish. Williams was increasingly asked to give readings around the country, and would do so as his health allowed. Julian Beck produced a successful off-Broadway run of Williams' play in 1959, which the poet was able to attend.

In 1961, Williams experienced another round of debilitating strokes, leading him to give up on his writing. He died on March 4, 1963. Williams' funeral in Rutherford was attended by his family and townspeople, as well as several younger writers from New York--including Gilbert Sorrentino, LeRoi Jones (Amiri Baraka) and Joel Oppenheimer--who had come to pay homage to the poet. Later that year, Williams was posthumously awarded the Pulitzer Prize for poetry for (1962) as well as the National Institute of Arts and Letters Gold Medal for poetry.