Born in Pittsburgh, Pennsylvania with the given name of Christopher Robison, Burroughs is the son of poet and writer Margaret Robison and the late John G. Robison, a former philosophy professor at the University of Massachusetts. He was raised in western Massachusetts, by his mother's psychiatrist's unorthodox family. He dropped out of school after sixth grade, but obtained a GED at age 17. He went on to a lucrative career in advertising, and subsequently became a successful writer after leaving advertising. Openly gay, his work centers around the fantastic and the mundane, which he delivers in a matter-of-fact style.

He now lives in New York City and Amherst, Massachusetts. He has been published in the New York Times, New York Magazine, The Guardian, The Times, and Out Magazine, and is a commentator for NPR's Morning Edition. In March 2003, he was named to Entertainment Weekly's 25 Funniest People in America list.

In June 2005, the Turcotte family filed a lawsuit against Burroughs at the Middlesex Superior Court in Cambridge, Massachusetts, claiming various family members and particularly Dr. Rodolph Turcotte, Burroughs's former legal guardian, were defamed and grossly misrepresented in the bestseller Running with Scissors as the eccentric Finch family.