Named after Major General Charles Cotesworth Pinckney, it was established to provide a nature and forest preserve for aesthetic and conservation purposes.

Permanent settlements did not occur until 1708 when Alexander Mackay, an Indian trader, obtained title to 200 acres (0.81 km2) of present-day Pinckney Island.

General Pinckney was a commander during the Revolutionary War, a signer of the United States Constitution, and, in 1804 and 1808, a presidential candidate for the Federalist Party.

The Bruces planted hardwoods and pine, built ponds to attract waterfowl and provide for irrigation, and placed 70 percent of the farm fields back into cultivation.

In 1954 Edward Starr and James Madison Barker, a distinguished MIT alumnus and early leader in the field of international business, purchased the islands.

A wide variety of land types are found on Pinckney Island alone: saltmarsh, forestland, brushland, fallow field and freshwater ponds.

Wildlife commonly observed on Pinckney Island include waterfowl, shorebirds, wading birds, raptors, neo-tropical migrants, and white-tailed deer, with large concentrations of white ibis, herons, and egrets.

Each year the refuge holds a one-day quota deer hunt to ensure that population numbers remain in balance with the surrounding habitat.