Garner was born near the village of Detroit in Red River County in eastern Texas. His parents were John Nance Garner III and his wife, the former Sarah Jane Guest. Garner studied at Vanderbilt University in Nashville, Tennessee, for one semester before dropping out and returning home. He was a member of the Pi Kappa Alpha fraternity. He eventually studied law, was admitted to the bar in 1890, and began practice in Uvalde, Uvalde County, Texas.