Born on November 6, 1969, Colson Whitehead was raised in Manhattan with three siblings. He attended Trinity, a private school, and then Harvard, where he studied English and Comparative Literature. At college, he befriended the poet Kevin Young. Following graduation from college, he worked at the Village Voice newspaper.

He has written several acclaimed novels. His first, The Intuitionist, published in 1999, won the Quality Paperback Book Club's New Voices Award and was a finalist for the PEN/Hemingway Award. This book is about elevator inspectors, including the first African American female inspector, in a fictional city modeled on New York. His next novel, John Henry Days, was published in 2001 and was a finalist for the Pulitzer Prize. In 2003, he published The Colossus of New York, a nonfiction work in which he discusses the way people approach and live in the ever-changing city.

His next novel, Apex Hides the Hurt (2006), was a recipient of the PEN/Oakland Award. In 2009, he published Sag Harbor, about two African American brothers spending the summer in Sag Harbor, a town in the Hamptons, largely without parental supervision. Zone One, published in 2011, is about a fictional New York following a pandemic that creates zombies. He then published The Noble Hustle: Poker, Beef Jerky & Death about his search for meaning at the World Series of Poker. In 2016, he published The Underground Railroad, about two slaves who escape northward via a literal underground railroad, not the actual, metaphorical "railroad" slave escape route of history. In 2019, he published The Nickel Boys, about an African American boy thrown into a hellish, abusive reform school called Nickel Academy in the 1960s.

He is married to a literary agent named Julie Barer and has two children. Whitehead has taught at several colleges, including Columbia, the University of Houston, and Princeton. He has won several other awards, including a Guggenheim Fellowship and a MacArthur Fellowship.