Highway 16 parallels Interstate 90 throughout its route and allows travelers the opportunity to experience Minnesota's Driftless Area.

The route passes through the Richard J. Dorer Memorial Hardwood State Forest in Fillmore and Houston counties.

Forestville Mystery Cave State Park is located near Highway 16 in Fillmore County.

The eastern terminus for Highway 16 is the Wisconsin state line at the Mississippi River outside La Crescent, concurrent with U.S.

[1] The only section of U.S. Highway 16 that remains in the present day is the east–west route between Rapid City, South Dakota and Yellowstone National Park in Wyoming.