The Second North Carolina Regiment was formed by order of the North Carolina Provincial Congress on September 1, 1775. Intended originally as one of two 500-man state defense units, the regiment was taken into the newly organized Continental Line on November 28, 1775. As a Continental Line unit, the regiment would be under the command of and paid by the Continental Congress rather than the NC provincial Congress.

The 1775 regulations called for a Continental Line Regiment to consist of 728 men divided into eight companies. Each company was to have a captain, two lieutenants, one ensign, four sergeants, four corporals, two drummers or fifers, and 76 privates.

From December 1775 to May 1777, the North Carolina Regiments remained in the South. The 2nd Regt. served in Virginia at the siege of Norfolk and also had detachments in North Carolina, South Carolina, and Georgia. They were assigned to guard the coast from British invasion and help round up the local Tories. Detachments of the 1st, 2nd, 3rd, and 4th NC Regiments were at the defense of Charleston, SC in June 1776.

In May 1777, the 2nd NC Regt. as part of the NC Brigade (which now consisted of nine regiments), was ordered north to join the troops under General Washington. The NC Brigade marched through Williamsburg and Richmond VA and paused at Alexandria to undergo inoculations for smallpox. By July the Brigade was in New Jersey. In July and August the troops were marched northward into New Jersey and then again south to Wilmington, DE to help counter a British thrust toward Philadelphia from the south.

The NC Brigade was at the battle of Brandywine, PA on September 11, 1777 but saw little action as it had been assigned to the reserves under General Greene. However, men from the NC Brigade serving in the recently organized Corps of Light Infantry did see heavy action during the battle as they defended Chad's Ford.

On October 3, 1777 the NC Brigade was in the battle of Germantown, PA where it again formed the reserve along with the Corps of Light Infantry. When called up, the Brigade saw intense fighting in which its commander, General Francis Nash, had his leg nearly shot off by a British cannon ball. Nash died on October 9th and was buried with full military honors along with several other NC officers killed in the battle.

The actions at Brandywine and Germantown left the NC Regiments in need of a commanding general as well as other field officer positions. Disagreements as to who should receive promotions caused many officers to resign their commissions and return to North Carolina. Eventually a system of promotions within regiments and the NC Brigade was established, however the command of the NC Brigade was given to General Lachlan McIntoch of Georgia as it went into winter quarters with the army at Valley Forge.

Troop returns for the NC Brigade at valley Forge for January 1778 give an idea of the suffering they endured. Out of 1188 men, 323 were listed as sick and 249 as unfit for duty for want of clothing. General Washington declared the NC Brigade was sicklier, for want of clothing and provisions, than any other unit at Valley Forge. The nine NC Regiments were so under strength they were consolidated into four regiments with the men of the 4th Regiment being reassigned to the 2nd Regiment.

In June 1778, the 2nd NC Regiment fought in the battle of Monmouth, NJ as part of Scott's division in LaFayette's brigade. During the remainder of the year, it was stationed at various posts around the Hudson River Highlands and at West Point. Although no major battles occurred, the men saw constant skirmishing with British foraging parties.

In July 1779, the Light Infantry companies of the 1st and 2nd NC Regiments were an important part of the assault on the British fort at Stoney Point, NY. The NC Light Infantry companies were commanded by Major Hardee Murfee of the 2nd NC Regiment. They were to make a diversionary frontal attack on the fort while the main columns, using only bayonet, attacked the fort from the flanks. In less than half an hour the fort was taken. The British lost 63 killed, 70 wounded, and 543 taken prisoner. American losses were light with only 15 killed and 83 wounded.

After Stoney Point, the NC Regiments were stationed on Constitution Island in the Hudson River at West Point. As it became clear the British would make the southern colonies their next objective, the NC Brigade was ordered south in November 1779. Marching in bitter winter, with snow at times three feet deep, the NC Brigade reached Charleston, SC on March 3, 1780. The British army laid siege to the city. After two months, and with no hope of relief, General Lincoln surrendered the city to the British. Over 5000 men of the colonies southern army were taken prisoner by the British. This included all the NC Continental Line Regiments then in the field.

In August 1781, a new 2nd NC Regiment was raised at Salisbury, NC. Poorly uniformed and armed largely with personal weapons, the new 2nd NC Regt. was soon in action at the Battle of Eutaw Springs, SC on September 8, 1781. During this engagement, the NC Regiments suffered greater losses than any other of the units engaged.

After Cornwallis surrendered to Washington at Yorktown, VA on October 19, 1781, the NC Regiments diminished rapidly as enlistments expired and it became evident that the war was drawing to a close. Near the end of 1782, most of the NC troops were ordered home. By June 1783, the remaining troops were furloughed at James Island, SC while awaiting the final signing of the peace treaty with Great Britain.

The 2nd North Carolina Regiment of the Continental Line was officially disbanded on November 15, 1783.