Born in Pasadena, California, he is a graduate of Brown University and the University of Chicago, and studied at Keio University in Tokyo.

He published his first novel, The Danish Girl, in 2000. It is based on the life of Lili Elbe, the first person to undergo sex reassignment surgery. The novel won the Rosenthal Foundation Award from the American Academy of Arts and Letters and the Lambda Literary Award. It was also a finalist for the New York Public Library's Young Lions Award and an American Library Association Award and was a New York Times Notable book. It is being developed into a feature film, starring and produced by Nicole Kidman. He published his first collection of short stories, The Rose City, in 2001. It won the Ferro-Grumley Award, was a finalist for the Lambda Literary Award, and was named one of the best books of the year by the Los Angeles Times. His second novel, Pasadena, was published in 2002 and was a New York Times bestseller. His fiction has been translated into a eighteen languages and published around the world to critical acclaim. In 2009, True West magazine, citing his West Coast heritage and interests, named him the Best Western Fiction Writer in the United States.

His third novel, The 19th Wife, was a New York Times bestseller, selling approximately 3/4 million copies around the world. The novel is about one of Brigham Young's plural wives, Ann Eliza Young, as well as polygamy in the United States today. Publishers Weekly called it "an exquisite tour-de-force" and Kirkus Reviews said it was "reminiscent of Wallace Stegner's Angle of Repose in scope and ambition", while the Los Angeles Times praised it by saying "it does that thing all good novels do: it entertains us." In 2009, British television talk show hosts Richard and Judy chose The 19th Wife for their on-air book club, making the book a #1 bestseller in the UK. A television movie adaptation will air on Lifetime on September 13, 2010. The novel was nominated for the Ferro-Grumley Award and the Utah Book Award and was named one of the best books of the year by Publishers Weekly.

Ebershoff is editor-at-large at Random House, where he edits a wide range of writers including novelists David Mitchell, Charles Bock, Gary Shteyngart, Phil LaMarche, Stefan Merrill Block, John Burnham Schwartz, poet Billy Collins, Nobel Peace Prize-winner Shirin Ebadi, journalists Azadeh Moaveni and Sonia Nazario, historian Hugh Thomas, actor Diane Keaton, and bestselling presidential scholar Ronald C. White, Jr.. Ebershoff was Jane Jacobs's editor on her final two books and was Norman Mailer's editor for the last five years of his life. Working with Truman Capote's estate, he oversees the Capote publications for Random House, and was the editor of The Complete Stories of Truman Capote, Summer Crossing, and Portraits and Observations. He was formerly the publishing director of Random House's classics imprint, the Modern Library. He also writes for Conde Nast Traveler.

Ebershoff has taught writing at NYU and Princeton, and currently teaches literature in the MFA program at Columbia University. He lives in New York City.