Pinckney Island NWR is archaeologically rich, with 115 prehistoric and historic sites identified. Analysis of the prehistoric sites indicate human occupation dating from the Archaic Period (8000 - 1000 BC), with intensive use during the Mississippian Period (1000 - 1500 AD).
Historic artifacts indicate that small scale, impermanent settlements were made on Pinckney by French and Spanish groups in the 16th and 17th centuries. Permanent settlements did not occur until 1708 when Alexander Mackay, an Indian trader, obtained title to 200 acres of Pinckney Island. By 1715, Mackay had acquired the rest of Pinckney and most of the other islands which comprise the present refuge. In 1736, Mackay's widow sold the islands to Charles Pinckney, father of General Charles Cotesworth Pinckney. General Pinckney was a commander during the Revolutionary War, a signer of the U.S. Consititution, and, in 1804 and 1808, a presidential candidate. Pinckney was an absentee landowner until 1804, when he moved to the island and began managing the property. The Pinckney family developed the islands into a plantation, removing much of the maritime forest and draining and tilling the fertile soil. By 1818, over 200 slaves were being used to produce fine quality long-staple sea island cotton on 297 acres; 386 slaves were mainted on the island by 1840.
The plantation flourished until the Civil War when it was occupied by Union Troops. Small skirmishes took place on Pinckney Island. The most significant incident occurred on August 21, 1862 when the Confederate Beaufort Light Artillary/11th Infantry attacked the camp of Company H, Third Regiment, New Hampshire Volunteers, killing four Union soldiers and wounding ten men (eight Confederate, two Union). Army records also reflect that black troops were recruited for the Union Army from the area. Five military (U.S. Colored Infantry) headstones are located in a cemetary on the northwest side of Pinckney Island indicating the possibility that slaves living on the plantation during the Civil War were recruited by the U.S. Army.
After the war, the plantation did not prosper, and by the 1930's, was virtually abandoned. In 1937, after over 200 years of Pinckney ownership, the plantation was sold to Ellen Bruce, wife of James Bruce, a New York banker who used the property as a hunting preserve. Hardwoods and pine were planted, ponds were built to attract waterfowl and for irrigation, and 70 percent of the farm fields were placed back into cultivation.
Edward Starr and James Barker puchased the islands in 1954 and continued to manage them as a game preserve. In 1975, the islands were donated to the U.S. Fish and Wildlife Service to be managed exclusively as a National Wildlife Refuge and as a nature and forest preserve for aesthetic and conservation purposes.