Bernstein was born in New York City to a Jewish family and attended the Bronx High School of Science and Harvard University, where he majored in Philosophy. Bernstein graduated Harvard College in 1972, and during his time there worked closely with Stanley Cavell, with whom he would write his thesis, a work that amalgamated analytical philosophy and avant-garde literature. His first book, Asylums, was published in 1975. Together with Bruce Andrews he edited the magazine L=A=N=G=U=A=G=E, which ran to 13 issues between 1978 and 1981. This was one of the most important outlets for Language poetry, and in 1984 he and Andrews published selected pieces from these 13 issues in The L=A=N=G=U=A=G=E Book. During this period, Bernstein also published three more books of his own poetry, Parsing (1976), Shade (1978) and Poetic Justice (1979), while earning a living as a freelance medical writer.

From 1989 to 2003, Bernstein was David Gray Professor of Poetry and Letters at the University at Buffalo, where he was co-founder and Director of the Poetics Program. He is also co-founder of The Electronic Poetry Center at Buffalo. He is currently the Donald T. Regan Professor of English at the University of Pennsylvania, where he is co-founder of the poetry audio archive PennSound. He has been the recipient of fellowships from the Guggenheim Foundation, the New York Foundation for the Arts, and the National Endowment for the Arts, and of the Roy Harvey Pearce/Archive for New Poetry Prize of the University of California, San Diego. Since 1980, he has published a further eighteen books of poetry, as well as editing a number of anthologies of prose and verse. Working with the composers Ben Yarmolinsky, Dean Drummond, and Brian Ferneyhough, he has written the libretti for five operas and has collaborated with a number of visual artists, including his wife, Susan Bee, Richard Tuttle, and Mimi Gross. Bernstein's Poetry has appeared in four editions of David Lehman's The Best American Poetry series, most recently in the 2008 edition. His work has also regularly appeared in Harper's Magazine, Poetry Magazine, and Critical Inquiry. While Bernstein has supported small presses throughout his career, he has also published on such mainstream academic presses as Oxford University Press, Harvard University Press, Northwestern University Press, and, most recently, The University of Chicago Press, which has published his last three major works. The publication of All the Whiskey in Heaven by Farrar, Straus, and Giroux in 2010 was his most commercial endeavor to date.

Bernstein appeared in the 2000 movie Finding Forrester, as Dr. Simon and in a series of 1999 TV commercials, with Jon Lovitz, for the Yellow Pages.

Full-length collections

• All the Whiskey in Heaven (Farrar, Straus, and Giroux, 2010)
• Girly Man (University of Chicago Press, 2006)
• Shadowtime (libretto for an opera with music by Brian Ferneyhough) (Los Angeles: Green Integer, 2005)
• With Strings (Chicago: University of Chicago Press, 2001)
• Republics of Reality: 1975-1995 (Los Angeles: Sun & Moon Press, 2000)
• Dark City (Los Angeles: Sun & Moon Press, 1994)
• Rough Trades (Los Angeles: Sun & Moon Press, 1991)
• The Sophist (Los Angeles: Sun & Moon Press, 1987; rpt. Cambridge, UK: Salt Publishing, 2004)
• Islets/Irritations (New York: Jordan Davies, 1983; rpt. New York: Roof Books, 1992)
• The Nude Formalism, with Susan Bee (Los Angeles: Sun & Moon Press, 1989; rpt Charlottesville, VA: Outside Voices, 2006)
• Controlling Interests (New York: Roof Books, 1980)
• L E G E N D, with Bruce Andrews, Steve McCaffery, Ron Silliman, Ray DiPalma (New York: L=A=N=G=U=A=G=E/Segue, 1980)
• Poetic Justice (Baltimore: Pod Books, 1979)
• Shade (College Park, MD: Sun & Moon Press, 1978)
• Parsing (New York: Asylum's Press, 1976)
• Asylums (New York: Asylum's Press, 1975)

Essays

• My Way: Speeches and Poems (Chicago: University of Chicago Press, 1999)
• A Poetics (Cambridge: Harvard University Press, 1992)
• Content's Dream: Essays 1975-1984 (Los Angeles: Sun & Moon Press, 1986; rpt Northwestern University Press, 2001)
• A Conversation with David Antin (New York: Granary Books, 2002)
• "Artifice of Absorption: An Essay" (Singing Horse Press, 1987) (Potes & Poets Press, 1988)

Editor

• Modern and Contemporary Poetics, Editor, with Hank Lazer, of a book series from the University of Alabama Press (1998 ... )
• Electronic Poetry Center, Editor, with Loss Pequeno Glazier (1995 ... )
• PENNSound, Director , with Al Filries (2003 ... )
• Poetry Plastique, ed. with Jay Sanders, exhibition catalog (New York: Granary Books / Marianne Boesky Gallery, 2001)
• 99 Poets/1999: A Special Issue of boundary 2 (Vol.26, No.1: Duke University Press, 1999)
• Close Listening: Poetry and the Performed Word (New York: Oxford University Press, 1998)
• LINEbreak: poetry interviews, host/co-producer. Twenty-six 30-minute programs, dist. Public Radio Satellite Program and on the Internet at the EPC (1995-96)
• Live at the Ear : A CD anthology of Ear Inn readings (Pittsburg: Elemenope Productions, 1994)
• "13 North American Poets", with Susan Howe, in TXT #31 (Le Mans, France and Bussels: 1993)
• The Politics of Poetic Form: Poetry and Public Policy (NY: Roof, 1990)
• Patterns/Contexts/Time: A Forum: 1989, with Phillip Foss in Tyuonyi (Sante Fe, 1990).
• "L=A=N=G=U=A=G=E Lines" in The Line in Postmodern Poetry, ed. Frank/Sayre (Urbana: University of Illinois, 1988)
• "43 Poets (1984)" in Boundary 2 (Binghamton, 1987)
• The L=A=N=G=U=A=G=E Book, with Bruce Andrews (Carbondale: Southern Illinois University Press, 1984)
• "Language Sampler" in Paris Review, No. 86 (New York: 1982)
• L=A=N=G=U=A=G=E, with Bruce Andrews (New York: 1978-1981); Vol. 4 co-published as Open Letter 5:1 (Toronto: 1982)
• Louis Zukofksy: Selected Poems, [American Poets Project], (Library of America; distributed by Penguin Putnam, Inc) (New York: 2006)

Translation

• Red, Green, and Black by Olivier Cadiot (Hartford: Potes & Poets, 1990)
• The Maternal Drape by Claude Royet-Journoud (Windsor, VT: Awede Press, 1984) 95)