Before the outbreak of World War II, Doss was employed as a joiner at a shipyard in Newport News, Virginia. He chose military service, despite being offered a deferment because of his shipyard work, on April 1, 1942, at Camp Lee, Virginia. He was sent to Fort Jackson in South Carolina for training with the reactivated 77th Infantry Division. Meanwhile, his brother Harold served aboard the USS Lindsey.
Doss married Dorothy Pauline Schutte on August 17, 1942, and they had one child, Desmond "Tommy" Doss Jr., born in 1946. Dorothy died on November 17, 1991 in a car accident (Desmond was driving and lost control of the vehicle). Doss remarried on July 1, 1993, to Frances May Duman.