The county was originally part of Orangeburg District, and in 1785 it was named Winton County. It was given its current name in 1798 when the County and its seat were named for Revolutionary War leader John Barnwell (1748-1800). Barnwell County, originally stretched from the Savannah River on the west almost to the Atlantic Ocean.

The South Carolina Railroad built in 1832, connected Charleston to Hamburg on the Savannah River. Hamburg was near Augusta, Georgia. This was the first steam railroad in the world. The railroad went through the middle of the county and two stops on the railroad created the towns of Blackville, South Carolina and Williston, South Carolina in the mid-nineteenth century.

Built in 1858, the sundial in Barnwell, South Carolina is the only remaining vertical freestanding sundial in the USA. It was surrounded by a parking lot in the 1960’s but in the 1990s the Town of Barnwell removed the parking lot, building a park, and made the sundial a focal point of a park.

Barnwell gave generously to the Confederate cause; the most distinguished was General Johnson Hagood who later as governor gave to the state. Soon after his election, one of Hagood's constituents asked him if he wished to be called "General" or "Governor". "Call me General," he said, with a twinkle in his eye, "I fought for that and begged for the other."

Barnwell was hated by General Sherman who felt that the town of Barnwell should be burnt to the ground since it carried the name of one of the most prominent politicians of the time who demanded South Carolina’s withdraw from the Union. When MAJ Kilpatrick’s Cavalry marched through Barnwell they used the Church of the Holy Apostles, erected in 1856, as a stable for his horses. The hoof prints are still visible in the floors. The medieval font in the church was used to water the horses. The church is on the National Register and is built of cypress wood from the local swamps.