By early 1776, prominent Loyalists in the South Carolina backcountry had been arrested, expelled, or driven into hiding. Many fled to the Cherokee towns in the southern Appalachians, where they were given refuge. A delegation of northern Indians had arrived in the Cherokee villages months earlier, persuading younger warriors to 'take up the hatchet' against the colonists who had been pressing further into Cherokee land for years. British Indian agent John Stuart tried to keep the Cherokee neutral; when he realized that was impossible, he tried to coordinate their attacks with British military operations instead. On July 1, 1776, the Cherokee went on the warpath. Henry Laurens wrote that they struck 'very suddenly, without any pretense to Provocation,' killing as many as 60 South Carolinians in the opening raids.

The timing favored the attackers. A British fleet had been anchored off Charleston since early June, and Continental Army General Charles Lee was tied down defending the coast - he had just helped repulse the British attack on Sullivan's Island on June 28. No relief was coming for the backcountry. Refugees streamed into frontier stockades. Lindley's Fort, a leftover from the Anglo-Cherokee War of the early 1760s, was hastily rehabilitated. Major Jonathan Downs arrived on July 14 with a militia company, bringing the defenders to about 150. The attack came the next morning. The Loyalist-Cherokee force had only muskets and tomahawks; the stockade walls held. When the attackers gave up on the fort and turned to easier targets in the surrounding countryside, Downs led a sortie. In a running fight he captured about 10 Loyalists. Two of the attackers were killed and 13 ultimately taken prisoner.

The Cherokee raids of spring and summer 1776 triggered a coordinated retaliation that historians sometimes call the Cherokee phase of the Revolution. North Carolina, South Carolina, Georgia and Virginia all sent militia. Between late July and early October, thousands of militiamen entered Cherokee territory and burned crops, villages and food stores systematically. The Cherokee abandoned their towns and fled west and south. The war the colonists waged on their indigenous neighbors was, by any measure, more destructive than what the British Crown was waging on the colonists themselves. The Cherokee people would spend the next generation displaced, regrouping, and eventually negotiating from a position of devastating weakness. The site of Lindley's Fort, just outside Laurens, was listed on the National Register of Historic Places. The stockade is gone. The fields where the painted attackers ran from Downs's sortie are now farmland and pasture in the rolling Piedmont.