Reed was born in Chattanooga, Tennessee, and grew up in Buffalo, New York, where he attended the University of Buffalo, a private university that became part of the state public university system after he left. The university awarded him an honorary doctorate in 1995.
In 1998, Reed spoke about his influences in an interview: "I've probably been more influenced by poets than by novelists — the Harlem Renaissance poets, the Beat poets, the American surrealist Ted Joans. Poets have to be more attuned to originality, coming up with lines and associations the ordinary prose writer wouldn't think of."
He moved to New York City in 1962 and co-founded with Walter Bowart the East Village Other, a well-known underground publication. He was also a member of the Umbra Writers Workshop, an organization among whose members were some that helped establish the Black Arts Movement and promoted a Black Aesthetic. Although Reed was never a participant in that movement, he has continued to research the history of black Americans, and while working on his novel, Flight to Canada, coined the term "Neo-Slave narrative." He used the term in 1984 in "A Conversation with Ishmael Reed" by Reginald Martin.
In 2005, Reed retired from teaching at the University of California, Berkeley, where he taught for thirty-five years, and is currently Visiting Scholar at California College of the Arts. He lives in Oakland, California, with his wife of more than 40 years, Carla Blank, the acclaimed author, choreographer, and director. His archives are located in Special Collections at the University of Delaware in Newark. Reed's author-maintained website appears at www.ishmaelreed.org.