Meredith was born in New York City to William Morris Meredith, Sr. and Nelley Keyser. He began writing while a college student at Princeton University where with his first volume of poetry Love Letter from an Impossible Land he was selected by Archibald MacLeish for publication as part of Yale Series of Younger Poets Competition. He graduated magna cum laude from Princeton in 1940 , writing a senior thesis on Robert Frost.
He worked briefly for the New York Times before joining the United States Navy as a flier. Meredith re-enlisted in the Korean War, receiving two Air Medals.
In 1988 Meredith was awarded the Pulitzer Prize for Poetry and a Los Angeles Times Book Award for Partial Accounts: New and Selected Poems and in 1997 he received the National Book Award for Effort at Speech. Meredith was also awarded a Guggenheim Foundation fellowship, the Harriet Monroe Memorial Prize, the Carl Sandburg Award, and the International Vaptsarov Prize in Poetry.
From 1964 to 1987 Meredith served as Chancellor of the Academy of American Poets.
From 1978 to 1980, Meredith was Consultant in Poetry to the Library of Congress, the position which in 1985 became the Poet Laureate Consultant in Poetry to the Library of Congress. He has the distinction of being the first gay poet to receive this honor.
Meredith taught at Princeton University, the University of Hawaii and at Connecticut College from 1955 to 1983. In 1983, he suffered a stroke and was immobilized for two years. As a result of the stroke he suffered with expressive aphasia, which affected his ability to produce language. Meredith ended his teaching career and could not write poetry during this period. He regained many of his language skills after intensive therapy and traveling to Britain for treatment.
A long time admirer of the Irish poet W. B. Yeats, in the summer of 2006 Meredith fulfilled a long-time ambition of visiting Yeats's spiritual homeplace of Sligo, Ireland. While there he also attended the renowned Yeats International Summer School, which attracts many renowned academics and admirers of Yeats to Sligo every summer.
Meredith died in New London, Connecticut, near his home in Montville, where he lived with his partner of 36 years, the poet Richard Harteis. A film about his life, Marathon, premiered on November 19, 2008 in Mystic, Connecticut.