Just east of William Street, it crosses over some railroad tracks of BNSF Railway.

Just east of 444th Avenue, it travels just south of the Baxter Slough State Public Shooting Area.

the highway then curves to the southeast to travel around the southwestern part of Clear Lake.

Just east of 458th Avenue, it crosses over the Big Sioux River and then travels just north of Castlewood.

East of 461st Avenue, it crosses over Stray Horse Creek and then curves to the north-northeast.

While traveling under the Interstate highway, it enters the west-central part of Deuel County.

Just to the east of 476th Avenue, it curves to the southeast to travel around the southeastern part of Clear Lake.

Just north of County Road 22A (CR 22A; 478th Avenue), the highway curves back to the east.

Just east of 184th Street, it reaches its eastern terminus, at the Minnesota state line.

[2] When SD 22 was originally established in the 1920s, its western terminus was at the Wyoming state line.