Established in 1932 as a migratory bird refuge, Cape Romain NWR encompasses a 22-mile segment of the southeast Atlantic coast. The refuge consists of 66, 267 acres which include a fascinating expanse of barrier islands, salt marshes, intricate coastal waterways, long sandy beaches, fresh and brackish water impoundments, and maritime forest.

The refuge's original objectives were to preserve in public ownership habitat for waterfowl, shorebirds and resident species. In recent years, objectives have expanded to include: managing endangered species, protecting the 28,000 acre Class I Wilderness Area, and preserving the Bulls Island and Cape Island forests and their diverse plant communities. Currently, the refuge is actively working to aid the recovery of the threatened loggerhead sea turtle.

The refuge headquarters and Sewee Visitor Center on US Highway 17 and the maintenance shop at Garris Landing are the only mainland sites. The remainder of the refuge is accessible only by boat. Points of interest include Bulls Island, Cape Island, and Lighthouse Island where two lighthouses, no longer operational, still stand.

Cape Romain NWR is one of four refuges within the South Carolina Lowcountry Refuges Complex. The Lowcountry, low lands which extend from the western sandhills to the Atlantic Ocean, is an area rich in natural and cultural history. Together, the South Carolina Lowcountry refuges total approximately 99,000 acres.