South Carolina Highway 16 (SC 16) is a state highway completely within Columbia. The highway runs 9.5 miles (15.3 km) in a backward C-shape.

SC 16 begins at an intersection with US 176 (River Drive) approximately 1 mile (1.6 km) east of the Broad River. In rapid succession is an intersection with US 21/US 321 (Main Street), an interchange with SC 277 (Northeastern Freeway), and an intersection with SC 555 (Farrow Road).

The road curves to the east and intersects US 1 (Two Notch Road). It then curves to the southeast and meets SC 12 (Forest Drive).

SC 16 then curves to the south and southwest to intersect US 76/US 378 (Devine Street).

The road then heads west and has a final bend, to the southwest to meet its terminus, at an intersection with SC 48, just south of the University of South Carolina.

The entire route is in Columbia, Richland County.