Desmond Doss was born in Lynchburg, Virginia, to William Thomas Doss (1893–1989), a carpenter, and Bertha Edward Doss (née Oliver) (1899–1983), a homemaker and shoe factory worker. His mother raised him as a devout Seventh-day Adventist and instilled Sabbath-keeping, nonviolence, and a vegetarian lifestyle in his upbringing. He grew up in the Fairview Heights area of Lynchburg, Virginia, alongside his older sister Audrey and younger brother Harold.

Doss attended the Park Avenue Seventh-day Adventist Church school until the eighth grade and subsequently found a job at the Lynchburg Lumber Company to support his family during the Great Depression.

Doss refused to kill an enemy soldier or carry a weapon into combat because of his personal beliefs as a Seventh-day Adventist. He consequently became a medic assigned to the 2nd Platoon, Company B, 1st Battalion, 307th Infantry, 77th Infantry Division.

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, from a car accident. Doss remarried on July 1, 1993, to Frances May Duman.

While serving with his platoon in 1944 on Guam and the Philippines, he was awarded two Bronze Star Medals with a "V" device, for exceptional valor in aiding wounded soldiers under fire. During the Battle of Okinawa, he saved the lives of 50–100 wounded infantrymen atop the area known by the 96th Division as the Maeda Escarpment or Hacksaw Ridge.

Doss said frequently after saving a wounded soldier: "help me get one more". This phrase motivated him to keep searching for soldiers

Doss was wounded four times in Okinawa and was evacuated on May 21, 1945, aboard the USS Mercy. Doss suffered a left arm fracture from a sniper's bullet and at one point had seventeen pieces of shrapnel embedded in his body. He was awarded the Medal of Honor for his actions in Okinawa.

After the war, Doss initially planned to continue his career in carpentry, but extensive damage to his left arm made him unable to do so. In 1946, Doss was diagnosed with tuberculosis, which he had contracted on Leyte. He underwent treatment for five and a half years – which cost him a lung and five ribs – before being discharged from the hospital in August 1951 with 90% disability.

Doss continued to receive treatment from the military, but after an overdose of antibiotics rendered him completely deaf in 1976, he was given 100% disability; he was able to regain his hearing after receiving a cochlear implant in 1988. Despite the severity of his injuries, Doss managed to raise a family on a small farm in Rising Fawn, Georgia.

After being hospitalized for difficulty breathing, Doss died on March 23, 2006, at his home in Piedmont, Alabama. He was buried on April 3, 2006, in the National Cemetery in Chattanooga, Tennessee. Frances died three years later on February 3, 2009, at the Piedmont Health Care Center in Piedmont, Alabama.

Hacksaw Ridge is a 2016 biographical war drama film directed by Mel Gibson and written by Andrew Knight and Robert Schenkkan, based on the 2004 documentary The Conscientious Objector. The film focuses on the World War II experiences of Desmond Doss, an American pacifist combat medic who, as a Seventh-day Adventist Christian, refused to carry or use a weapon or firearm of any kind. Doss became the first conscientious objector to be awarded the Medal of Honor, for service above and beyond the call of duty during the Battle of Okinawa. Andrew Garfield stars as Doss, with Sam Worthington, Luke Bracey, Teresa Palmer, Hugo Weaving, Rachel Griffiths, and Vince Vaughn in supporting roles.