For many years, Hardeeville billed itself as the "Lowcountry Host" due to the prevalence of lodging and traveler-oriented facilities along U.S. Highway 17 and later Interstate 95. In recent years, the city has expanded its economic focus due to high population growth. According to Census estimates, Hardeeville posted the highest population growth rate of any municipality in South Carolina, growing 53.4 percent from 2010 to 2014.

The earliest European settlement in the region was Purrysburg, a former Swiss Huguenot settlement founded in 1732 on the banks of the Savannah River, about two miles (3 km) northwest of the current city's center. The settlement ultimately failed as disease and competition from growing Savannah proved too much for the local settlers to overcome. Many left the immediate area, moving elsewhere in the Lowcountry region (including a new hamlet called Switzerland) or upriver to the new communities of Augusta and Hamburg, though some remained.

The area saw some skirmishes between Union and Confederate forces during the Civil War. The Charleston and Savannah Railway (today's CSX railway) was considered a prized possession and major strategic goal for Union forces. In an effort to defend the railroad, the Battle of Honey Hill was one of the last battles won by southern forces in late 1864, shortly before General William Sherman attacked South Carolina after his "March to the Sea" in Georgia.

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