Harleyville takes its name from the Harley family, who owned much of the land that became the town. William "Cow Bill" Harley held substantial property in the area and raised cattle for the Charleston market. In 1885 he sold a right of way across his land to the Eutawville Railroad, which built a line between Pregnall,s and Eutaw Springs and made Harleyville a regular stop. The railroad spurred development of the lumber industry, and the town was incorporated in 1893. In the 20th century, as automobile travel grew more popular, Harleyville again benefited from its location along one of South Carolina's main thoroughfares. South Carolina Highway 2, now Highway 178, was the first hard-surfaced road in Dorchester County, and when it was completed in 1932 it extended from upstate South Carolina to Charleston. Known as South Carolina's Main Street, Highway 2 helped Harleyville remain a trading center for surrounding farms. Interstate 26 replaced South Carolina Highway 2 as a main highway in the 1960s.