The entire route from Eau Claire to the city limits of Superior is a four lane divided highway.

From there, U.S. 53 crosses Interstate 90 and becomes a freeway bypass of Onalaska and Holmen before proceeding north to Eau Claire as a two-lane roadway.

The interchange with Interstate 94 at Eau Claire begins a freeway / expressway stretch for U.S. 53 north to the city limits of Superior.

The c. 2006 freeway in Eau Claire bypasses most of the city, alleviating congestion on the original route (signed now as both Business U.S. 53 and Hastings Way).

Other smaller towns between Eau Claire and Superior (Minong and Solon Springs) were bypassed in a similar manner.

I-535/US 53 has an interchange with I-35 in Duluth, known locally as the "Can of Worms"; it features a pair of left exits from I-35, a stoplight and lane drops over the I-35 bridge.

[10] A bypass around Virginia was completed in 1964 and opened to traffic that November;[11] State Highway 135 was extended along the previous alignment through the city.

Previously, from 1934 to 2004, this same section of U.S. 53 was a narrow two-lane roadway that had proceeded up the hill to a seven-legged intersection that had included Duluth's Skyline Parkway.

[15] There were three rerouting options proposed:[16] The East route was selected for the project and construction began in November 2015,[17] with the realignment reaching completion in 2017.

The primary development planned is infrastructure-related, specifically, a highway project hoped to spur economic development in northwestern Wisconsin and northeastern Minnesota by widening U.S. Highway 53 to full expressway standards from Chippewa Falls, Wisconsin to International Falls, Minnesota.

On the south end of the corridor, the connection to Interstate Highway 94 is a 7.5-mile (12.1 km) stretch through the Eau Claire-Chippewa Falls conurbation.

After years of legal and political wrangling, the decision was made in the late 1990s to bypass the current route, rather than to convert the present highway to freeway standards.

[19] At present, with the exception of 3.5 miles (5.6 km) stretch within the city of Duluth (Piedmont Avenue and Trinity Road), the route is completed as an expressway as far north as the city of Cook, leaving approximately 73 miles (117 km) of the route to International Falls to be converted to expressway standards.