Keyes was born in Meridian, Mississippi, as John Gregory Keyes. He received degrees in anthropology from Mississippi State University and the University of Georgia before becoming a full-time writer.
He is famous for his tetralogy The Age of Unreason, a steampunk/alchemical story featuring Benjamin Franklin and Isaac Newton. He wrote the Babylon 5 Psi Corps trilogy, a history of the Psi Corps and a biography of Psi Corps member Alfred Bester.
In 2003 he began a fantasy series titled The Kingdoms of Thorn and Bone, the first volume of which was The Briar King. The second book in the series The Charnel Prince was published in 2004 and the third, The Blood Knight, was published in July 2006. His fourth and final book of the quartet, The Born Queen, was released in March 2008.

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