In the 1670s, Dr. Henry Woodward was chosen by the recently organized colony of Carolina to befriend the Creek and turn them on the Spanish. It was the intent of the English settlers to drive the missionaries and their garrisons of seasoned Spanish regulars from the coast south of Charles Town, as well as those who had moved inland. Hernando de Soto was not the only adventuresome soul to wander through what is now the South Carolina backcounty. The Spaniards Juan Pardo and Pedro de Torres explored much what is today South Carolina, while Tristan de Luna and others also explored deep into Georgia, Alabama and Tennessee.

By 1685, Dr. Henry Woodward and the Creek had successfully eliminated all the Spanish missions along the coast and internally, including the Spanish mission at the confluence of the Flint River and the Chattahoochee River. From this point onward, the Creek were in constant contact with the English, first with traders who wanted goods for coastal whites, then settlers who wanted land. It was an association the Creek would come to regret.

In 1674, under the leadership of Dr. Henry Woodward, the colony began trading with the Westoe Indians on the Savannah River. The Westoes told him that eight days journey west lived the "Chorakae Indians with whom they are at continual warrs". The Westoe's were to become the middlemen in trade between the Carolinians and the Cherokees in what Woodward called a trade in "drest deare skins furrs and young Indian Slaves." Similarly, the Occaneechi would, for years, serve as middlemen between the Cherokees and Virginians.