Isolated from the rest of South Carolina by swamps and rivers through the 19th century, Dillon County was created from larger Marion County in 1910. The county was named for James W. Dillon, an Irish immigrant who helped bring the Atlantic Coastline Railroad to the region in the late 19th century. The county developed as an agricultural region known for timber, tobacco and cotton. The county seat is the city of Dillon, known today for South of the Border, a nearby state-line interstate stop and tourist attraction, and as the hometown of Federal Reserve Chairman Ben Bernanke.

Constructed in 1911, the Dillon County Courthouse is a beaux-arts, brick and stone, Neo-classical structure featuring a colossal central Ionic portico with dual flanking wings. It is one of six courthouses in South Carolina designed by architect William Augustus Edwards who designed numerous public buildings in the early 20th century, including the Withers Building at Winthrop University and Currell College at the University of South Carolina.

The Dillon County Courthouse is considered to be one of Edwards's foremost architectural achievements. The building is listed on the National Register of Historic Places. An exhibition of photographs tracing Dillon County history is featured on the courthouse top floor.