The most common proposed etymology of the toponym Ninety Six is a reference to the distance in miles between the location and the Cherokee town of Keowee.

The first land battle (the siege of Savage's Old Fields) of the war fought in South Carolina took place at Ninety Six on November 19–21, 1775; then major Andrew Williamson of the Ninety-Six District Regiment of militia tried to recapture ammunition and gunpowder taken by Loyalists; outnumbered, he finally reached a truce with them.

[4][5] The village became a Loyalist stronghold early in the war, though the backcountry of the Carolinas was populated both by those loyal to crown and by partisans.

From May 22 to June 18, 1781, newly appointed Southern Department commander of the Continental Army, Major General Nathanael Greene led 1,000 troops in a siege against the 550 Loyalists defending the fort in the village.

Additional off-road trails weaving through the woods lead to Star Fort Pond, an old unidentified cemetery (believed to be a slave cemetery from post-colonial times), and to the graves of Major James Gouedy, a trader influential in the founding of Ninety Six, and Major James Mayson, who captured a significant gunpowder cache to be used by the Americans.