The oldest artifacts found at Palmetto Bluff, stone tools made by Paleoindians, date to 10,000 B.C. Following these early visitors, generations of Native Americans came to Palmetto Bluff to harvest oysters and fish in the rivers, and to hunt and gather in the forests. Today, archaeologists find oyster shells, bones, and fragments of clay pots and stone tools as evidence of the prehistoric people. However, by 1562, when Jean Ribaut arrived at Parris Island, the land of Palmetto Bluff appeared to have been uninhabited.
In 1730, British naval officer Admiral George Lord Anson purchased the property. However, Anson never lived here. Instead, after sailing around the globe and capturing Spanish galleons, he returned to England to enjoy his fame and fortune. In 1757, Anson divided his May River estate into parcels that were sold as individual plantations.
In the antebellum era, Palmetto Bluff was comprised of 21 plantations. One of the plantation owners was Thomas Fenwick Drayton, commander of the Confederate soldiers at Fort Walker on Hilton Head Island during the Battle of Port Royal. In this battle, General Drayton faced his own brother, Captain Percival Drayton, commander of a Federal gunboat. The Union navy easily defeated the Confederate forces and General Drayton was forced to order a retreat.