With the outbreak of the Civil War, John Pemberton enlisted in the Confederate States Army. He joined the 12th Regiment Georgia Volunteer Cavalry, reflecting his commitment to the Confederate cause.

Pemberton was severely wounded in April 1865 during the Battle of Columbus, Georgia, one of the last battles of the Civil War. He was struck in the chest by a saber, an injury that caused him chronic pain and eventually led to his morphine addiction.

The severe wound Pemberton sustained during the war had lasting effects on his health. The chronic pain he experienced led to his dependence on morphine, a common painkiller at the time, which played a crucial role in his later experiments and eventual creation of Coca-Cola as a morphine alternative.