^Wisconsin 21 gets started at its western point of beginning in Sparta, at Wisconsin Highway 16, July 2025.
Wisconsin Highway 21 is a pretty long east-west route from Sparta to Oshkosh, in the middle of Wisconsin. Wisconsin Highway 21 begins at an intersection on the north side of Sparta, just a bit north of Wisconsin Highway 16 and Interstate 90. Wisconsin Highways 27 and 71 are riding the north-south roadway at this intersection. From here, Wisconsin Highway 21 angles northeastward to pass through Fort McCoy. It soon straightens out to an east-west route, passing along the north side of Tomah, where it meets Interstate 94. It meets Wisconsin Highway 80 at Necedah, and then, it meets Interstate 39 at Coloma. In Wautoma, Wisconsin Highway 21 meanders through town, utilizing pavement shared by Wisconsin Highway 73 and Wisconsin Highway 22. Farther east, Wisconsin Highway 21 meets Wisconsin Highway 116 in Omro. The last stretch of Wisconsin Highway 21 proceeds beyond Omro and takes people to Oshkosh, where Highway 21 ends at US Route 45.