U.S. Route 16 (US 16) is an east–west United States Highway between Rapid City, South Dakota and Yellowstone National Park in Wyoming.

As of 2004, the highway's eastern terminus is at a junction with Interstate 90/U.S. Route 14 (I-90/US 14), concurrent with I-190, in Rapid City, South Dakota. The western terminus is the east entrance to Yellowstone National Park, concurrent with US 14 and US 20.