In the U.S. state of Wisconsin, U.S. Route 51 (normally called U.S. Highway 51, Highway 51 or US 51) runs north–south down the central part of the state. It enters from Illinois at Beloit, and runs north to its northern terminus in Hurley where it junctions with US 2.

From Beloit, US 51 passes through Janesville, and Stoughton, then passes through the east side of Madison as a side route paralleling to the west of Interstate 39 and Interstate 90. North of Madison, US 51 parallels the interstate on the east side passing through De Forest and Portage. The route joins I-39 north of Portage. They stay joined until I-39 ends at WIS 29. Along the way, the route bypasses the small communities of Endeavor, Packwaukee, Westfield, Coloma, Hancock, Plainfield, Plover, and Whiting prior to arriving at Stevens Point. Proceeding north from Stevens Point, the highway bypasses Knowlton, Mosinee, and Rothschild where I-39 terminates at WIS 29 East interchange. US 51 continues on with WIS 29 for 5 miles (8.0 km) bypassing Schofield, then proceeding into Wausau where WIS 29 splits to the west. US 51 continues as a freeway to Merrill, passing Brokaw along the way.

The section of US 51 from Portage at its junction with I-39 to Merrill is built to Interstate highway standards. The freeway in the Wausau area was not originally fully up to interstate standards, but a project to upgrade the freeway to full interstate standards in the area was recently completed. The upgrades in the Wausau area replaced all of the existing 1963-era low clearance overpasses; upgraded the WIS 29 East, CTH N, CTH NN, Sherman St, WIS 52, and Bridge St interchanges; and constructed a free-flow interchange for WIS 29 West. US 51 exists as an expressway from CTH K on the north side of Merrill further north to CTH S south of Tomahawk with 6 grade-level intersections. CTH S begins another stretch of Freeway with 4 grade-separated interchanges before the highway becomes a two-lane road just north of US 8 at the Oneida County line.

The highway passes through Minocqua, Manitowish Waters, and Mercer on its northwest trek toward Hurley and its terminus â€” at its junction with US 2.

Prior to 1926, what is now US 51 was State Trunk Highway 10.

US 51 was upgraded to a full freeway over a period of 25 years from Merrill to Portage. The freeway continues around Portage to the West as I-39 (originally as WIS 78) to connect with I-90 and I-94 while US 51 continues along surface roads into and through Portage. In the 1990s, US 51 was designated as I-39 from its junction with WIS 29 eastbound in Wausau to where it left the freeway at Exit 92 in Portage. US 51 remained cosigned with I-39 along this entire stretch of road. Further expansion of the highway northward took place in 2000 when the highway was upgraded to an expressway up to US 8.

The Wisconsin mileage of US 51 is designated by the state as the Korean War Veterans Memorial Highway.