The Salkehatchie River Basin encompasses eleven (11) watershed and 1,021 square miles in South Carolina. It originates in the Upper Coastal Plan and flows through the Lower Coastal Plain and Coastal Zone regions. This river basin covers approximately 653,606 acres. There are roughly 1,012 stream miles and 2,928 acres of lake waters in the Salkehatchie River Basin.

The Salkehatchie River originates near the city of Barnwell and accepts drainage from Turkey Creek and Whippy Swamp before merging with the Little Salkehatchie River to form the Combahee River Basin, which empties into the St. Helena Sound and the Atlantic Ocean. Prior to the confluence, the Little Salkehatchie River accepts drainage from Lemon Creek, Buckhead Creek, and Willow Swamp.