Berryman was born John Smith in McAlester, Oklahoma. At age twelve, after his family had moved to Florida, Berryman's father shot himself to death outside his son's window. His surname comes from his mother's second marriage, after the family moved to New York. Berryman was educated at Columbia and Cambridge Universities and himself became an influential teacher at Harvard, Princeton, and Minnesota. But he struggled with alcoholism and madness throughout his life. In the end, he leapt to his death from a bridge in Minneapolis.

Although he wrote short poems, a long poem and a 385-poem sequence, Homage to Mistress Bradstreet (1956) and The Dream Songs (1964-1968), are his major achievements. In the later work, Berryman performs, exhibits, and burlesques his psychic struggles and his attitudes toward contemporary culture through a series of personae. Stylistically and rhetorically inventive, they are quite unlike anything else in modern poetry.