The Yamasee War was a conflict fought in South Carolina from 1715 to 1717 between British settlers from the Province of Carolina and the Yamasee, who were supported by a number of allied Native American peoples, including the Muscogee, Cherokee, Catawba, Apalachee, Apalachicola, Yuchi, Savannah River Shawnee, Congaree, Waxhaw, Pee Dee, Cape Fear, Cheraw, and others. Some of the Native American groups played a minor role, while others launched attacks throughout South Carolina in an attempt to destroy the colony.

Native Americans killed hundreds of colonists and destroyed many settlements, and they killed traders throughout the southeastern region. Colonists abandoned the frontiers and fled to Charles Town, where starvation set in as supplies ran low. The survival of the South Carolina colony was in question during 1715. The tide turned in early 1716 when the Cherokee sided with the colonists against the Creek, their traditional enemy. The last Native American fighters withdrew from the conflict in 1717, bringing a fragile peace to the colony.

The Yamasee War was one of the most disruptive and transformational conflicts of colonial America. For more than a year, the colony faced the possibility of annihilation. About 70 percent of South Carolina's settlers were killed, making the war one of the bloodiest wars in American history. The Yamasee War and its aftermath shifted the geopolitical situation of both the European colonies and native groups, and contributed to the emergence of new Native American confederations, such as the Muscogee Creek and Catawba.

The origin of the war was complex, and reasons for fighting differed among the many Indian groups that participated. Factors included the trading system, trader abuses, the Indian slave trade, the depletion of deer, increasing Indian debts in contrast to increasing wealth among some colonists, the spread of rice plantation agriculture, French power in Louisiana offering an alternative to British trade, long-established Indian links to Spanish Florida, power struggles among Indian groups, and recent experiences in military collaboration among previously distant tribes.