William W. Witherspoon was living in Mississippi by the early 1860s. In March 1862, he received a commission as a junior 2nd lieutenant in Company A of the 36th Mississippi Infantry. He was promoted to major and then to colonel soon afterward. The regiment took part in the siege of Corinth, the siege of Vicksburg, the Atlanta campaign, and the Battle of Franklin. He surrendered as part of the Vicksburg garrison on July 4, 1863. He was eventually exchanged, and he returned to command. He died in the Battle of Franklin on November 30, 1864.