Englander grew up as part of the Orthodox Jewish community in West Hempstead, New York. He attended the Hebrew Academy of Nassau County for high school, and is an alumnus of the Binghamton University, and the Iowa Writers' Workshop at the University of Iowa.

Since the publication of For the Relief of Unbearable Urges, he has received a number of awards, including a Guggenheim Fellowship, the Bard Fiction Prize, and a fellowship at the Dorothy and Lewis B. Cullman Center for Scholars and Writers at the New York Public Library. Three of his short stories have appeared in editions of The Best American Short Stories. "The Gilgul of Park Avenue" appeared in the 2000 edition, with guest editor E.L. Doctorow; and "How We Avenged the Blums" appeared in the 2006 edition, guest edited by Ann Patchett.

The Ministry of Special Cases, the long-awaited follow-up to his debut, was released on April 24, 2007. The novel is set in 1976 in Buenos Aires during Argentina's "Dirty War" and has been described as "an impeccably paced, historically accurate novel which is alternatively side-splitting and frighteningly macabre."

Englander lives in New York. He teaches fiction as a part of CUNY Hunter College's Master of Fine Arts Program in Creative Writing.

Nathan Englander is currently a Fall 2009 Mary Ellen von der Heyden Fellow for Fiction at the American Academy in Berlin and working on his second novel Coward: A Novel.