On September 1, 1775, North Carolina's 1,000 continentals were arranged in two regiments, each consisting of three field officers, an adjutant, and ten companies. The companies assembled at Salisbury beginning in October. 

On November 28, 1775 the Continental Congress ordered both North Carolina regiments reorganized on the new Continental eight-company structure. It went on to authorize a third regiment on January 16, 1776 and two more regiments on March 26, 1776.

The Continental Congress accepted the 6th North Carolina Regiment on 7 May (retroactively) and subsequently adopted three troops of light horse and an artillery company which the colony had raised during the summer.

Instead of a seventh regiment, five independent companies of state troops were authorized to defend specific points. Two were standard-sized companies, but the other three each had only sixty privates. On May 3, 1777, a 24-man company was added to garrison a frontier fort.

Thus, the 6th North Carolina Regiment was formed on April 13, 1776. It was formed with eight companies from men from the Wilmington and Hillsborough Military Districts, which made up nearly one-half the state, including much of the backcountry. They were organized at Halifax, NC, under the command of Colonel Alexander Lillington, hero of the Battle of Moore's Creek Bridge.

When ready to march north to join the main army, they were instead called south to defend Charleston against a suspected second assault in 1776 (after the lst attack was repulsed in June). In the meantime, Colonel Lillington stepped down due to ill health. He was replaced by Colonel Gideon Lamb. The British did not return in 1776. The NC Line spent a miserable winter near Charleston without the supplies promised by South Carolina.

The 6th Regiment marched north in the spring and joined the main army, brigaded under General Francis Nash. They were in the battles of Brandywine and Germantown, being at the Chew House in the latter and serving as rear guard for the American withdrawal during which Gen. Nash was mortally wounded. They were noted by one diarist as having captured sixteen guns during the attack, but having had to abandon them in the retreat.

They wintered at Valley Forge in General Lachlan Macintosh's Brigade. The NC troops were noted by Washington to be the poorest supplied of all the destitute men there. Their desertion rate was ten percent, the lowest in an Army that averaged 18 percent. It was a long way home.

In the reductions of 1778, the 6th Regiment was merged with the lst NC Regiment, assuming the lower regimental number. The supernumerary officers of the 6th Regiment were sent home to NC to recruit. All troops recruited by the 6th Regiment for the next several years were taken immediately into the other NC units. The 6th Regiment ceased to exist officially in early 1781.

In the meantime, the men of the 6th Regiment, now the lst Regiment, served at Monmouth, being engaged early and again late in the day, and in the Hudson Highlands. Some of them took part in the frontal assault by NC troops of Wayne's Light Infantry on Stony Point. In November 1779 they were ordered south to Charleston during the worst winter of the war. They arrived in time to take part in the defense and, along with the Virginians, took part in the only sortie during the siege.

On 12 May 1780, they went into captivity with the fall of Charleston. Many of them were sent to the prison hulks in the harbor while others were imprisoned on John's Island. The 6th Regiment disappeared from the field and on paper.