Mendelsohn was born in Long Island. He graduated with a B. A. in Classics from the University of Virginia, which he attended from 1978 to 1982 as an Echols Scholar, and received his M. A. and Ph. D. in Classics from Princeton University, where he was a Mellon Fellow in the Humanities.
Upon completing his Ph.D. in 1994, Mendelsohn began a career in journalism in New York City. His review-essays about books, films, and theater appear frequently in The New York Review of Books. Between 2000 and 2002 he was the weekly book critic for New York Magazine, and his work has appeared as well in The New Yorker, The New York Times, Esquire, The Paris Review, The New Republic, and many other publications.
In 2005 Mendelsohn was the recipient of a Guggenheim Fellowship for a translation of Cavafy's "Unfinished" poems, with commentary. His other honors include the National Book Critics Circle Award for Excellence in Book Reviewing (2000) and the George Jean Nathan Prize for Drama Criticism (2002).
Mendelsohn's academic speciality is Greek (especially Euripidean) tragedy; he has also published scholarly articles about Roman poetry and Greek religion. From 1994 to 2002, he was a Lecturer in the Classics department at Princeton University. Currently, he holds the Charles Ranlett Flint Chair in Humanities at Bard College. In April 2008, he was the Richard Holbrooke Distinguished Visitor at the American Academy in Berlin, Germany. In the Spring of 2010, he will be a Critic-in-Residence at the American Academy in Rome.
Mendelsohn is the brother of the film director Eric Mendelsohn, photographer Matt Mendelsohn and journalist Jennifer Mendelsohn.
The Elusive Embrace, a memoir entwining themes of homosexual identity, family history, and Classical myth and literature, was published in 1999 by Alfred A. Knopf, and was named a New York Times Notable Book of the Year, and a Los Angeles Times Best Book of the Year. It was published in a French translation as L'étreinte fugitive by Flammarion in January, 2009.
Gender and the City in Euripides' Political Plays, a scholarly study of Greek tragedy, published by Oxford University Press in 2002, with a paperback edition published in 2005.
The international bestseller A Search for Six of Six Million, the story of the author's worldwide search over five years to learn about the fates of relatives who perished in the Holocaust, was published in the US in September, 2006. The Lost won the National Book Critics Circle Award for Memoir/Autobiography, the National Jewish Book Award for Biography/Autobiography, the Salon Book Award, a Barnes and Noble "Discover" Award, and the American Library Association Sophie Brody Medal for Outstanding Achievement in Jewish Literature. Published in over a fifteen countries, it was awarded the 2007 Prix Médicis in France, the 2008 Premio WIZO-ADEI in Italy, and was shortlisted for the Duff Cooper Prize in the UK.
How Beautiful It Is And How Easily It Can Be Broken, a collection of his essays on literature and the arts, mostly from The New York Review of Books, was published in August, 2008 and named a Publishers Weekly Best Book of 2008.
C. P. Cavafy: Collected Poems and C. P. Cavafy: The Unfinished Poems, published simultaneously in March 2009. The latter volume, which is the first English translation of the thirty unfinished drafts that Cavafy left when he died in 1933, is based on the reconstructions of the Italian Neohellenist Renata Lavagnini. Mendelsohn's Cavafy translation was a Publishers Weekly Best Book of 2009.