During the American Revolutionary War, the newly proclaimed United States competed with the British for the allegiance of Native American nations east of the Mississippi River. Most Native Americans who joined the struggle sided with the British, hoping to use the war to halt further colonial expansion onto Native American land. Many native communities were divided over which side to support in the war. For the Iroquois Confederacy, the American Revolution resulted in civil war. Cherokees split into a neutral (or pro-American) faction and the anti-American Chickamaugas, led by Dragging Canoe.

Frontier warfare during the American Revolution was particularly brutal, and numerous atrocities were committed on both sides. Noncombatants of both races suffered greatly during the war, and villages and food supplies were frequently destroyed during military expeditions. The largest of these expeditions was the Sullivan Expedition of 1779, which destroyed more than 40 Iroquois villages in order to neutralize Iroquois raids in upstate New York. The expedition failed to have the desired effect: Native American activity became even more determined. 

The British made peace with the Americans in the Treaty of Paris (1783), and had ceded a vast amount of Native American territory to the United States without informing the Native Americans. The United States initially treated the Native Americans who had fought with the British as a conquered people who had lost their land. When this proved impossible to enforce (the Native Americans had lost the war on paper, not on the battlefield), the policy was abandoned. The United States was eager to expand, and the national government initially sought to do so only by purchasing Native American land in treaties. The states and settlers were frequently at odds with this policy.