Santee National Wildlife Refuge was established on May 5, 1941 to alleviate the loss of natural waterfowl and wildlife habitat caused by the construction of hydro-electric projects on the Santee and Cooper Rivers. Stretching for eighteen miles along the northern shore of Lake Marion, the refuge protects 15,095 acres within the upper coastal plain region of Clarendon County, South Carolina. From open waters to closed hardwood canopies - from freshwater marshes to cultivated fields - from cypress swamps to upland pines - and practically everything in between - Santee has them all. Since the key to wildlife diversity is habitat diversity, it's easy to understand why so many different species call this refuge home. Unique natural and cultural resources found on the refuge include a Carolina Bay and the Santee Indian Mound which was used as both a ceremonial and burial mound. British troops erected Fort Watson atop the Mound during the Revolutionary War only to have it taken by General Francis Marion's troops in April of 1781.

The office/visitor center is located just off of U. S. Highway 301/15, seven miles south of Summerton, S. C. Visitors may take Exit 102 on Interstate 95 and follow the signs.