From there it passes several miles north and east of the tourist town of Deadwood before entering Meade County, going just to the west of Sturgis.

The route then enters Pennington County, where it passes through the northern edge of Rapid City, gateway to the Black Hills and the nearest passing to Mount Rushmore National Memorial, as well as other scenic attractions including Custer State Park and the Needles Highway.

It is in Lyman County, at exit 212 in Vivian, that the highway provides its closest link to the capital of Pierre, along US 83, some 35 miles (56 km) north.

East of Brandon and northeast of Valley Springs, it then ends its trip through South Dakota of 413 miles (665 km) before entering Minnesota and Rock County, just west of the towns of Beaver Creek and Manley.

The four-lane Interstate replaced old US 16 as the main road connecting Rapid City and Sioux Falls.

Much of Old US 16 remains intact; however, I-90 has absorbed sections and likewise has reshaped the economies of many southern South Dakota towns.

[7] The exit was closed and removed as a result of the South Dakota Department of Transportation (SDDOT)'s efforts to move traffic away from a potential crash site at the end of the Ellsworth AFB runway.

[8] Local citizens and officials feared the lack of entrances which access the Ellsworth AFB would cause traffic issues and moving businesses from near the old exit would cause some to close and affect tax revenue.