The route was officially added to the Interstate Highway System on April 7, 2015, and connects Milwaukee and Green Bay with the Fox Cities.

The Interstate is 175.00 miles (281.64 km) long and located almost entirely within the state of Wisconsin and is completely concurrent with a slightly adjusted alignment of US 41 to its termination in Green Bay.

[8] At the end of October 2012, WisDOT submitted I-41 to AASHTO for consideration at their fall Special Committee meeting, where it was conditionally approved on November 16, 2012, pending FHWA concurrence.

[17][needs update] The redesignation to Interstate status also makes the route subject to the Highway Beautification Act, meaning current advertising billboards along the Milwaukee-to-Green Bay portion of the road can no longer be upgraded or enlarged nor can new signs be added.

[18] Beginning in early 2024, WisDOT plans to start several projects to improve I-41 in the Appleton//Fox Cities metro area between Neenah and De Pere.

The projects will include widening the Interstate from two to three lanes in each direction on a 23-mile-long (37 km) stretch between Appleton and De Pere, upgrading interchanges, reconstructing bridges, and repaving sections of the freeway, along with the new South Bridge Connector project adding a new Fox River span south of De Pere with an I-41 interchange.