Simeon Cornelius Wilkerson was born around 1839 in Alabama to Presley Wilkerson and Eliza Foster. His father was a farmer who owned $5,000 of real estate in 1850. He grew up and attended school in Tuscaloosa County, Alabama, before enrolling at the University of Alabama in 1856. He eventually began work as a dentist.
He received a commission as a 1st lieutenant in the 18th Alabama Infantry during the Civil War. He eventually earned a promotion to captain. Union forces captured him at Missionary Ridge on November 25, 1863, and he was exchanged on December 5.
Wilkerson married Nancy Bryson on April 9, 1863, in Noxubee County, Mississippi. He settled in Tuscaloosa, Alabama, after the war and resumed his work as a dentist. By 1870, he owned $2,500 of real estate and $2,000 of personal property. He died sometime after 1880.