It splits from US 16 in the Black Hills of the southwestern part of the U.S. state of South Dakota.

The eastern terminus is at an interchange with US 16 called Keystone Wye south of Rapid City.

The route passes through Keystone, the Mount Rushmore National Memorial, the Norbeck Wildlife Management Area and Black Elk Wilderness within Black Hills National Forest, and Custer State Park (including State Game Lodge and Legion Lake), before rejoining the parent highway.

US 16A is famous for its scenic, one-lane tunnels aligned to frame the faces on Mount Rushmore, its "pigtail bridges", and its sections of divided highway but with single (and narrow) lanes on each roadway.

At the highest point of the byway, on the summit of Iron Mountain, there is a small memorial to Governor Norbeck.