Before turning to popular fiction, Mayor held several jobs, both in the US and in France, working as an editor, researcher for Time–Life books, photographer and journalist. He also worked for the University of Texas Press in the late 1970s, where, as Special Projects Editor, he found and caused to be published The Book of Merlyn, the hitherto barely known conclusion to T. H. White's famous The Once and Future King.
Mayor's first novel, Open Season, was published in 1988, and was the first of his popular Joe Gunther mystery series. Since then, a new novel has been published every year, typically in the fall. Mayor devotes much of the year researching various components of his novel, in addition to working as a death investigator for the Vermont State Medical Examiner's office and as a deputy for the Windham County Sheriff's Dept. He also volunteers for his local Fire Department and EMT squad.