South Carolina Highway 16 (SC 16) is a 9.6-mile-long (15.4 km) primary state highway in the U.S. state of South Carolina that exists mostly within Columbia in Richland County.

The first SC 16 was an original state route from SC 2 (today US 176) in Columbia, north into North Carolina, continuing as NC 16; it connected the cities and towns of Ridgeway, Winnsboro, Chester, York, and Clover.

In 1927, US 21 was assigned between Columbia and Chester; the following year SC 16 was removed from that section.

The third and current SC 16 eventually resurrects part of its previous route.

Reappearing in 1964, as a new primary routing, it traversed from its current northern terminus at US 176 east to US 76/US 378/SC 760.