The Pocotaligo Massacre represented a critical moment in the escalating tensions between European settlers and Native American tribes in early 18th century South Carolina. In the early months of 1715, colonists became increasingly anxious as disputes over trade practices and land encroachment intensified with the Yamasee and affiliated tribes. These conflicts were exacerbated by growing resentment towards the colonists' demands for more land, alongside a significant decline in the deer population, which diminished traditional trade routes based on fur trade.

On April 15th, 1715, violence erupted at the Pocotaligo River, where a group of colonists, feeling threatened, engaged in a deadly confrontation with Yamasee warriors. The skirmish resulted in the deaths of both colonists and Native Americans, igniting a broader conflict known as the Yamasee War. The aftermath of the Pocotaligo Massacre saw the Yamasee tribes mobilizing their alliances, including Creek and Cherokee tribes, against the colonists, who were now facing a united front from the Native nations.

The Yamasee War began as a struggle for survival for the Native Americans who sought to protect their territory from colonial encroachment. The war lasted until 1717 and resulted in severe repercussions for both sides, deeply affecting the socio-political landscape of the region. This conflict underscored the fragility of colonial-Native relations and was a precursor to further tensions and confrontations in the coming decades as settlers pushed further into Native American territories, fundamentally altering the balance of power in the Southeast United States.