U.S. Route 53 is a north–south U.S. highway that runs for 403 miles (649 km) from La Crosse, Wisconsin to northern Minnesota. It is the primary north–south route in northwestern Wisconsin, serving as a vital link between I-94 at Eau Claire, Wisconsin and the city of Duluth, Minnesota. The entire route from Eau Claire to the city limits of Superior, Wisconsin is a four lane divided highway. The highway's northern terminus is at the Fort Frances-International Falls Bridge in International Falls, Minnesota, at the U.S.-Canadian border. Its southern terminus is in La Crosse, Wisconsin, at U.S. Highway 14.

Der U.S. Highway 53 (kurz US 53) ist ein United States Highway in den Vereinigten Staaten. Er verbindet die U.S. Highways 14 und 61 im Westen von La Crosse im Bundesstaat Wisconsin mit den kanadischen Grenze nahe Fort Frances.