The county was much larger in its early days but the relatively newer counties of Aiken, Bamberg and Aliendale acquired parts of the original Barnwell County.

Like much of this area, Barnwell County grew with the introduction of the South Carolina railroad. The railroad linked Charleston with the old town of Hamburg on the Savannah River. Because of the railroad, the Barnwell County towns of Williston and Blackville grew up alongside the railroad tracks in the mid-1800s. Although trains no longer run through these towns, the history of the railroad is still apparent.

Barnwell County was home to several influential state politicians, namely Sen. Edgar A. Brown (1888-1975), state Speaker of the House Solomon Blatt (1895-1986) and former governor Joseph E. Harley (1880-1942). Collectively, they were known as the "Barnwell Ring."

After World War II, the Cold War of the 1950s created a new industry — an atomic industry — in Barnwell County.

A large portion of the county, as well as parts of Aiken and Allendale counties, were used by the U.S. Department of Energy to create the Savannah River Site, locally referred to in its beginning as "the bomb plant."

SRS became a major employer for many Barnwell County residents. Although SRS doesn't employ as many people as it did initially, the site is still a major economic factor in the county. Also other ancillary businesses located in the county to help serve the specialized needs of SRS as well.

Now Barnwell County is comprised of 548 square miles of land with an approximate population of 23,404, according to a 2004 U.S. Census estimate. The population has remained fairly stable in the last several years, showing a less than 1 percent decrease since 2000.

Demographically, there are about 9,021 households in the county, with 55.2 percent of the population as Caucasian and 42.6 being African-American, according to 2000 U.S. Census survey data.