It consists of two segments of highway signed as east–west but physically traveling north–south from the Georgia state line near Mountain Rest to Beech Island.

It is part of a continuous highway separated by a 17.5-mile (28.2 km) stretch through Augusta, Georgia.

Once south of Anderson, it switches into a two-lane rural road through Antreville, around Abbeville, and through McCormick.

Along the banks of Lake Strom Thurmond, it eventually crosses over a non-dammed section of the Savannah River near Augusta, Georgia.

[9] Established as an original primary route in 1922, SC 28 went northwest from Allendale, through Ellenton, to Beech Island.

In 1940, SC 28 was extended southeast to Gardens Corner as new primary routing; however, eight years later the extension was dropped, truncated back in Yemassee.

In 1951 or 1952, SC 28 between Beech Island and Allendale was cut off by the establishment of the Savannah River Site.

was a business loop that used to follow original SC 28 through the downtown Seneca; it has since been decommissioned.

is a five-point-zero-zero-zero-mile (8.047 km) business route that follows the original path of SC 28 through downtown Anderson via Clemson Boulevard and Main Street.

was a business loop used to follow original SC 28 through downtown Abbeville; it has since been decommissioned.

was an alternate route that provided direct access to Ellenton's town center from the mainline.