South Dakota Highway 21 (SD 21) is a 9.470-mile (15.240 km) state highway in south-central Hamlin Countym South Dakota, that connects Lake Norden and Hayti.

Just south of 189th Street, it begins to parallel the eastern part of Lake Marsh.

In the west-central part of the town, it turns right onto Main Avenue and heads to the east.

Between 2nd and 3rd streets, it passes a U.S. post office and the Hayti Fire Hall.

At an intersection with 4th Street, SD 21 turns left and heads north again.