Eisenberg grew up in suburban Chicago, Illinois, and moved to New York City in the late 1960s. She was an editorial assistant at The New York Review of Books in 1973. Her longtime companion is actor-writer Wallace Shawn. She teaches at the University of Virginia.
Eisenberg has written four collections of stories: Transactions in a Foreign Currency (1986), Under the 82nd Airborne (1992), All Around Atlantis (1997), and Twilight of the Superheroes (2006). Her first two story collections were republished in one volume as The Work (So Far) of Deborah Eisenberg (1997). The Rea Award for the Short Story - Deborah Eisenberg All four short-story collections were reprinted in 2010 in The Collected Stories of Deborah Eisenberg (2010)
She has also written a play, Pastorale, which was produced at Second Stage in New York City in 1982. Eisenberg has written for such magazines as The New York Review of Books, The New Yorker, and The Yale Review.
Eisenberg was the recipient of the Rea Award for the Short Story in the year 2000, an award granted for significant contribution to the short story form. She has also been the recipient of such awards as a Whiting Writers' Award, a Guggenheim Fellowship, and three O. Henry Awards. In 2009, she was awarded a MacArthur Fellowship.
Ben Marcus, reviewing Twilight of the Superheroes for The New York Times Book Review, called Eisenberg "one of the most important fiction writers now at work."