Following North Carolina's secession from the Union, Vance returned home to Asheville and in June, 1861 joined a volunteer unit, the "Rough and Ready Guards." He was elected Captain of the unit, which was sent to Virginia and became Company F, 14th North Carolina Troops. Shortly thereafter, an opportunity presented itself and Vance, determined to lead, left his homegrown unit to become Colonel of the newly organized 26th North Carolina Troops.
Though excited about the prospect of leadership, Vance realized that his military experience was not adequate to the task. He gladly turned over the details of discipline and drill to Lt. Col. Henry King Burgwyn, Jr., a well-educated, professionally-trained officer. This cemented Vance's popularity with his men; Burgwyn, the disciplinarian was disliked, but Vance was beloved. Said one soldier,
"In the first place he had the keenest sympathy with his men. They soon came to feel that Colonel Vance loved them and made their troubles his own. In the next place Colonel Vance was able to inspire his men with the belief that he had confidence in them." (Covered With Glory by Rod Gragg, p. 11-12)
In the wake of the Federal capture of Hatteras Island in August 1861, the 26th was posted to the North Carolina coast. Burgwyn moved the troops to Morehead City on September 2, 1861 ahead of Vance, and set about establishing camp on Bogue Banks, near Fort Macon. After shifting their campsite a number of times, the regiment settled into winter quarters on the mainland, across the sound from the Banks.
In February 1862, the 26th moved to New Bern as part of a concentration of Confederate forces to oppose an attack by Gen. Ambrose Burnside's Federal force. The Burnside Expedition, as it is now known, captured Roanoke Island and took control of the Albemarle Sound before turning to make a push southward. Confederate general Lawrence O'Bryan Branch positioned the 26th on the right end of the defensive line, in hastily constructed earthworks near the railroad. Vance anchored the center of the position, while Burgwyn manned the far right of the line. On March 14, as the Federals advanced, the center of the Confederate line, to the left of the position held by the 26th, was breached, forcing Vance to give an order for his troops to retreat. In the confusion of battle over seventy men from the regiment were captured or missing, five were killed, including two officers, and ten more were wounded.
What started as an organized retreat turned to near panic when the 26th reached the Trent River. General Branch's retreating troops had already set fire to the bridges, forcing the 26th to reroute their retreat to Brice's Creek. Vance nearly drowned trying to cross the deep swift creek on his horse and was saved only by some quick thinking and decisive action on the part of his troops. Burgwyn took control of the regiment, found a number of small boats to use, and began the process of ferrying his men across the creek. All the while, Federal forces were bearing down on the Confederates. Burgwyn refused to cross until all of the men were safely on the opposite bank. Because of his coolness under duress and bravery, the attitude of the men toward the lieutenant colonel changed dramatically.
With New Bern lost to the Federals, the Confederate forces converged on Kinston to regroup. Newspaper accounts of the Battle of New Bern generally portrayed the 26th favorably, and the regiment's reputation as a solid military unit was cemented. However, the same accounts tended to exaggerate Vance's role in the action. Vance did not dispute these inaccuracies and probably promoted them to some extent. Burgwyn certainly disagreed, going so far as to privately blame Branch and Vance for the defeat at New Bern.
Confederate forces were reorganized at Kinston and the 26th was placed under the command of Gen. Robert Ransom. Vance issued public calls for uniforms, equipment, and volunteers to replace that which was lost at New Bern. Due to the regiment's solid reputation and an enlistment bonus, Vance was flooded with new recruits, as well as material support from the citizens of North Carolina.
Many of the soldiers in the 26th had signed on for twelve month enlistments, which were close to expiring as the unit reorganized at Kinston. Using his superior abilities as a politician and speaker, Vance was able to convince most of the soldiers to reenlist. Vance's natural abilities assured his reelection as the regiment's colonel. Burgwyn was also reelected, based on his newfound respect among the troops.
On June 19, 1862 Vance announced to his troops that the brigade had been summoned to Virginia. Ransom's Brigade was chosen by Gen. Robert E. Lee to join the Army of Northern Virginia. The 26th was destined for the Seven Days Campaign, in defense of the Confederate capital of Richmond.
After being involved in several skirmishes, the 26th was called into action on July 1 at the Battle of Malvern Hill. Through the din of battle, the regiment became disoriented and the officers soon realized they were off course. Some Confederates were retreating past them, prompting Burgwyn to grab one fleeing soldier and force him at sword point to lead the 26th toward the front lines. By the time the regiment reached its lines and shifted into battle formation, it was nearly dark. They were quickly pinned down by heavy Federal artillery fire. The Federal guns fell silent at about 10:00 p.m. and the 26th was ordered to quietly withdraw at 11:30. Casualties suffered by the 26th were relatively light.
Malvern Hill proved to be Vance's last military action, as he was soon elected governor of North Carolina. He left the unit in August and Burgwyn, promoted to colonel, was given command of the regiment. Because of political differences between Burgwyn and Ransom, the 26th was transferred to Gen. James Johnston Pettigrew's Brigade. Vance returned home to rest and to recover his strength before taking office as governor in September, 1862.