Andrew Sean Greer, the child of two scientists, was born in Washington, D.C.. He studied writing with Robert Coover and Edmund White at Brown University, where he was the commencement speaker at his own graduation. After years in New York working as a chauffeur, theater tech, television extra and unsuccessful writer, he moved to Missoula, Montana, where he received his Master of Fine Arts from The University of Montana, from where he soon moved to Seattle and two years later to San Francisco where he now lives. He is currently a fellow at the New York Public Library Cullman Center. He is an identical twin.

While in San Francisco, he began to publish in magazines before releasing a collection of his stories, How It Was for Me. His stories have appeared in Esquire, The Paris Review, The New Yorker and other national publications, and have been anthologized most recently in The Book of Other People, and The PEN/ O. Henry Prize Stories 2009.

His first novel, The Path of Minor Planets, was published in 2001.

His second book, The Confessions of Max Tivoli, came out in 2004. Writing in The New Yorker, John Updike called the book “enchanting, in the perfumed, dandified style of disenchantment brought to grandeur by Proust and Nabokov.” Mitch Albom then chose The Confessions of Max Tivoli for the Today Show Book Club and it soon became a bestseller. The story of a man aging backwards, it was inspired by the Bob Dylan song "My Back Pages." Though similar in theme, it is related neither to the Fitzgerald short story nor the film "The Curious Case of Benjamin Button."

The New York Times has written that in his third novel, The Story of a Marriage, Greer ascends “to the heights of masters like Marilynne Robinson and William Trevor.”