It was the main unit involved in the successful defense of Fort Moultrie at the Battle of Sullivan's Island. This battle saved Charleston from invasion for the next several years, and handed the British fleet their first loss in over a century. When the flag designed by the fort's commander, Colonel William Moultrie, was shot down, one of the regiment, William Jasper, grabbed it and held it aloft, rallying the troops until a stand could be provided.
This battle was vital to the entire war, and became symbolic of liberty in South Carolina. Its date is known as Carolina Day in the state, and the palmetto logs the regiment used for the fortress were added to the Moultrie Flag used to rally the troops, creating the Flag of South Carolina.
The regiment saw action at the Siege of Savannah and the Siege of Charleston. The regiment was captured by the British Army at Charleston on May 12, 1780, together with the rest of the Southern Department. The regiment was disbanded on November 15, 1783.