Powdersville is a census-designated place (CDP) in Anderson County, South Carolina.

In 1859 a powder mill was established in present-day Powdersville by John Bowen.

During the American Civil War, the area was used to store gunpowder though Columbia remained the primary production site of the state's powder.

The southeast border of the CDP is formed by Interstate 85, a six-lane highway with access to Powdersville via exits 39 and 40.

Greenville, the largest city in the region, is 8 miles (13 km) to the northeast.

As of the 2020 United States census, there were 10,025 people, 3,515 households, and 2,570 families residing in the CDP.

Public education in Powdersville is administered by Anderson County School District One.