U.S. Highway 45 runs north–south through the eastern and northern portions of the state of Wisconsin. Also called Highway 45, it runs from the state line with Illinois near the village of Bristol in Kenosha County to the Michigan state line at the town of Land O' Lakes in Vilas County, a total of about 305 miles (491 km).

U.S. Route 45 in the state of Illinois is a major north–south U.S. Highway that runs from the Brookport Bridge over the Ohio River at Brookport north through rural sections of eastern Illinois and then through the suburbs of Chicago to the Wisconsin state line east of Antioch. This is a distance of 428.99 miles (690.39 km). US 45 is the longest numbered route in Illinois.