 William L. Mayo was born in Prestonsburg, Kentucky, in 1861, and was educated at Prestonsburg Seminary, Cedar Bluff Academy in Tazewell County, Virginia, and Central Normal College in Danville, Indiana; he had planned to attend Indiana University until financial difficulties prevented him from doing so.He worked as a teacher and principal at Cedar Bluff Academy before taking a public school position in Denver, although he resigned upon arriving and learning that the school was integrated.Mayo then moved to Pecan Gap in Delta County, Texas, in 1886, where his aunt and uncle lived; he began teaching at the local public school, and by 1889 had become superintendent of nearby Cooper's public school system.