William A. Quarles, the son of Garrett and Mary J. (Poindexter) Quarles, was born near Louisa Court House in Louisa County, Virginia. When he was five years old, his family moved to rural Christian County, Kentucky, and then later to Clarksville, Tennessee. He was educated at home as a youth, and attended the University of Virginia until his father's untimely death forced him to return home to manage the family estate. He studied law and was admitted to the bar in 1848, and established a law practice in Clarksville. Interested in politics, he was a Democratic presidential elector in 1852, supporting Franklin Pierce's candidacy.