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Highway 181 is called Wauwatosa Road from its northern terminus to the Milwaukee County line.
South of County Line Road in Milwaukee, it becomes 76th Street, a major commercial and industrial corridor on Milwaukee's northwest side.
At Center Street near Wauwatosa, the road becomes Wauwatosa Avenue. In downtown Wauwatosa, the highway is routed onto the local streets Harmonee Avenue and Harwood Avenue before resuming on Glenview Avenue south of downtown.
In West Allis, Glenview Avenue becomes 84th Street, and the highway continues south to its terminus at West Greenfield Avenue (State Highway 59).
The section of Highway 181 from Interstate 94 to Greenfield Avenue travels along the west side of Wisconsin State Fair Park.