Saylor's best-known work is his Roma Sub Rosa historical mystery series, set in ancient Rome.

The novels' hero is a detective named Gordianus the Finder, active during the time of Sulla, Cicero, Julius Caesar, and Cleopatra.

A Twist at the End, featuring O. Henry, is set in Austin in the 1880s and based on real-life serial murders and trials (the case of the so-called Servant Girl Annihilator).

Saylor contributed autobiographical essays to three anthologies of gay writing edited by John Preston, Hometowns, A Member of the Family, and Friends and Lovers, and prior to his novel-writing career he published gay erotic fiction under the pen name Aaron Travis.

Saylor has lived with Richard Solomon since 1976; they registered as domestic partners in San Francisco in 1991 and later dissolved that partnership in order to legally marry in October 2008.