At the outbreak of the war, Jenkins was elected colonel of the 5th South Carolina Infantry. He led them into action at the Battle of First Manassas. Subsequently, he formed the Palmetto Sharpshooters, which he led into battle during the Peninsula Campaign at the battle of Seven Pines. In July 1862 he received a promotion to brigadier general. Although severely wounded at the Battle of First Manassas, he accompanied the 1st Corps to Chickamauga, where he served as a division commander. He participated in the Knoxville Campaign before he returned to Virginia to lead his old brigade at the Battle of the Wilderness. During this action, he was struck down in the same volley that wounded Gen. James Longstreet. Several hours later, he died from his wound.