Berkeley County was named for two of the Lords Proprietors of South Carolina -- Lord John Berkeley (d. 1678) and Sir William Berkeley (d. 1677). The county was originally named in 1682, and at one time it included the parishes of St. John, St. James-Goose Creek, St. James-Santee, St. Stephen, St. Thomas, and St Denis.

In 1769 the area became part of Charleston District, and it did not become a separate county again until 1882. The county seat was Mount Pleasant from 1882 until 1895, when it was moved to Monks Corner.

The area was settled in the late seventeenth century by English and French Huguenot planters and their African slaves. The French Huguenot influence is rooted in the area and can be seen by many of the surnames from that area, i.e., Bordeaux, Deveaux, Dupree, Gaillard, Gourdin, Mazych, Ravenell, and Rembert, and from place names, i.e., Bethera, Bonneau, Huger, Ravenell, and Rembert.

Rice was the most profitable crop grown by planters up to the time of the Civil War. Many of the old rice plantations are now covered by waters of Lake Moultrie, which was built in the 1940s as part of the Santee-Cooper hydroelectric project.