Charles Bernstein was born in New York City to Jewish parents and grew up near Central Park. His father worked in the garment industry. Bernstein attended the Bronx High School of Science, where he edited the school newspaper. He entered Harvard in 1968, the same year he met his future wife, Susan Bee. During his university years, Bernstein protested against the Vietnam War and worked on the freshman literary magazine. He also published Writing, a photocopied magazine. Bernstein wrote his senior thesis on two writers who influenced his later poetry, Gertrude Stein and Ludwig Wittgenstein. In 1973, Bernstein received the William Lyon Mackenzie King Fellowship at Simon Fraser University in British Columbia, Canada. From there, Bernstein moved to Santa Barbara, California, where he worked part-time at a community free clinic. Bernstein spent about twenty years working as a medical and healthcare editor and writer; this experience has partially informed his poetry. Bernstein also served as the associate director of the Comprehensive Employment and Training Act (CETA) Artists Project.
In 1975, Bernstein and Bee moved back to New York; they married two years later and had two children, Emma and Felix. Bernstein became very active in the New York poetry scene. Bernstein and his wife founded Asylum’s Press, which published his first two books, Asylums and Parsing. In 1978, he and Ted Greenwald established the Ear Inn series, which went on to be a significant venue for emerging writers. That same year, Bernstein and Bruce Andrews created L=A=N=G=U=A=G=E magazine. Although its production value was quite low—the books were photocopied and stapled together without covers—the magazine was an important publication. In 1984, three years after the magazine had ceased publication, Bernstein and Andrews selected pieces from the thirteen issues and published them as The L=A=N=G=U=A=G=E Book.
Bernstein was awarded a University of Auckland fellowship in 1986, which helped him develop his international reputation. In 1999, Bernstein played Dr. Simon in a number of television commercials with Jon Lovitz for the Yellow Pages. The following year, he appeared in the film Finding Forrester (2000), which starred Sean Connery. Bernstein has been writer-in-residence or visiting faculty at Columbia, Princeton, Brown, and Temple universities; Bard College; the New School for Social Research; Queens College; and the University of California, San Diego.
At the State University of New York at Buffalo, Bernstein served as David Gray Professor of Poetry and Letters and as director of the poetics program from 1990 to 2003. He cofounded the Electronic Poetry Center with Loss Glazier. In 2003, Bernstein became the Donald T. Regan Professor of English and Comparative Literature at the University of Pennsylvania, where, with Al Filreis, he was confounder and coeditor of PENNsound, an archive of recorded poetry.