Sexton was born in Norton, Massachusetts in 1928, and spent most of her life near Boston. In 1945, Sexton began attending a boarding school, Rogers Hall, in Lowell, Massachusetts. She eloped in 1948 with Alfred Muller Sexton, known as "Kayo." Before their divorce in the early 1970's, she had two children with Kayo: Linda Gray Sexton, later a novelist and memoirist, and Joyce Sexton. She suffered from depression for most of her life. Sexton's first breakdown took place in 1954. After a second breakdown in 1955, Anne met Dr. Martin Orne at Glenside Hospital, who encouraged her to take up poetry writing, and she enrolled in her first poetry workshop, with John Holmes as the instructor. After the workshop, Sexton experienced quick success with her poetry, with her poems accepted by . Sexton's poetic life was further encouraged by her mentor, W.D. Snodgrass, whose poem, "Heart's Needle" encouraged her to write "The Double Image", a poem significant in expressing the multi-generational relationships existing between mother and daughter.

While working with John Holmes, Sexton encountered Maxine Kumin, whom she became good friends with throughout the rest of her life. Kumin and Sexton rigorously critiqued each others work, and wrote four children's books together.

She attended a poetry workshop with Sylvia Plath, taught by Robert Lowell. Later, Sexton herself taught workshops at Boston College, Oberlin College, and Colgate University. Anne Sexton is the modern model of the confessional poet, perhaps begun by the publication of ; Sexton wrote about menstruation, abortion, masturbation, and adultery before such issues were even topics for casual discussion, helping redefine the boundaries of poetry. Sexton modeled for a stint at Boston's Hart Agency. Astonishingly, she never garnered any collegiate accolades or even a degree, thus testifying her affinity to and brilliance with poetic language.

She committed suicide in 1974. She is buried at Forest Hills Cemetery Crematory in Jamaica Plain, Boston, Massachusetts. British musician Peter Gabriel wrote a song, "Mercy Street", dedicated to Anne Sexton in 1986. Diane Middlebrook wrote a biography , came from her meeting with a Roman Catholic priest who, although he refused to administer the last rites, did tell her: "God is in your typewriter," which gave the poet the desire and willpower to continue living and writing for some more time. In 1967, she won the Pulitzer Prize for her collection, which was