South Carolina was outraged over British tax policies in the 1760s that violated what they saw as their constitutional right to "no taxation without representation". Merchants joined the boycott against buying British products. When the London government harshly punished Massachusetts for the Boston Tea Party, South Carolina's leaders joined 11 other colonies (except Georgia) in forming the Continental Congress. When the British attacked Lexington and Concord in the spring of 1775 and were beaten back by the Massachusetts Patriots, South Carolina rallied to support the American Revolution. Loyalists and Patriots of the colony were split by nearly 50/50. Many of the South Carolinian battles fought during the American Revolution were with loyalist Carolinians and the part of the Cherokee tribe that allied with the British. This was to General Henry Clinton's advantage. His strategy was to march his troops north from St. Augustine, Florida, and sandwich George Washington in the North. Clinton alienated Loyalists and enraged Patriots by attacking a fleeing army of Patriot soldiers who posed no threat. Enslaved Africans and African Americans chose independence by escaping to British lines where they were promised freedom.

Combined Continental Army and state militia forces under the command of Major General Nathanael Greene regained control of much of South Carolina by capturing the numerous interdependent chain of British held forts throughout the State. One-by-one, the British and Loyalists were surrounded in the capital of Charles Town and became completely dependent on supplies by sea. After preliminary peace terms had been agreed, the British evacuated Charles Town on December 14, 1782, a day now officially designated as "South Carolina Independence Day". Greene was awarded a Congressional Medal and numerous other official awards from the State of South Carolina for his leadership in liberating the state and for restoring an elected government.

On October 8, 1780, at Kings Mountain, American Colonel Isaac Shelby led a body of North and South Carolinians and attacked British Major Patrick Ferguson and his body of American loyalists on a hilltop. America's first major poet, William Cullen Bryant, described the home field advantage that led to the Patriot victory in one of his poems. This was a major victory for the Patriots, especially because it was won by militiamen and not trained Continentals. It provided a great swing of momentum for the moderate "Overmountain Men" who had grown tired of British brutality. Kings Mountain is considered to be the turning point of the revolution in the South, because it squashed any significant further recruitment of Loyalists, and compelled Cornwallis to temporarily abandon North Carolina.

That December, General Nathanael Greene arrived with an army of Continental troops. When Greene heard of Tarleton's approach, he sent Brigadier General Daniel Morgan and his backwoodsmen over the Appalachian Mountains to stop him. On January 17, 1781, the two forces met at a grassy field with widespread hardwoods, reeds, and marsh in a well-known cattle grazing area called Cowpens. Pickens and his guerilla soldiers joined Morgan directly before the battle. Morgan still felt they were not strong enough to take on Tarleton's trained troops and wanted to cross a river that would separate them from the British and secure them a chance to retreat. Pickens convinced Morgan that staying on the British side of the river would force his men to fight it out in what some historians consider the best-planned battle of the entire war. The Patriots defeated the British and later battles at Hobkirk's Hill and Eutaw Springs would further weaken the British.

Fighting continued throughout 1781 in the backcountry, where patriot and loyalist militias alike looted homes and killed civilians. One of the most infamous is William "Bloody Bill" Cunningham's "Bloody Scout," who terrorized homes and massacred dozens of Whigs.[citation needed]

In December 1782, the British evacuated Charles Town. The overjoyed residents changed the name to "Charleston" because it sounded "less British."