In an attempt to recruit colonists into the backcountry of Colonial South Carolina, the colonies' legislature established immense land grants along the upper reaches of the Great Pee Dee River in 1736 and 1737. The region was initially settled by Welsh colonists who migrated to South Carolina from Delaware and Pennsylvania. The Welsh settlers and their descendants carved a new life out of the South Carolina wilds in communities such as Welsh Neck, Society Hill and Darlington.

The region was part of St. David's Parish in 1768, Cheraws District in 1769, and then became Darlington County following the Revolution in 1785. In 1800, a court district was established at Darlington, and a reorganized Darlington County was established in 1868, 1888 and 1902.

In 1806, the first courthouse at this site was destroyed by fire - a blaze reportedly set by a female defendant attempting to destroy court records. The original courthouse was replaced by a structure designed by South Carolina architect Robert Mills, but it too burned in 1866. The existing Darlington County Courthouse, which replaced earlier structures, was completed in 1964.