U.S. Route 41, also U.S. Highway 41 (US 41), is a north–south United States Highway that runs from Miami, Florida to the Upper Peninsula of Michigan. Until 1949, the part in southern Florida, from Naples to Miami, was US 94, which presently has the hidden designation of State Road 90 (SR 90) in addition to its signed number.

The highway's northern terminus is east of Copper Harbor, Michigan, at a modest cul-de-sac near Fort Wilkins Historic State Park at the tip of the Keweenaw Peninsula in the state's Upper Peninsula. Its southern terminus is in the Brickell neighborhood of Downtown Miami at an intersection with Brickell Avenue (US 1). It closely parallels Interstate 75 (I-75) from Naples, Florida, all the way through Georgia to Chattanooga, Tennessee.

In Florida, US 41 is paralleled by Interstate 75 all the way from Miami to Georgia (on the northern border), and I-75 has largely supplanted US 41 as a major highway.

Between Miami and Naples, US 41 cuts across the Florida peninsula, running through the vast Everglades wilderness. This section has been designated a National Scenic Byway. The byway runs east–west through the Big Cypress National Preserve, skirting the northern border of the Everglades National Park for about 20 miles (32 km). The part of the highway between Tampa and Miami is known as the Tamiami Trail (derived from the combination of Tampa and Miami, the road's two termini), thus, this section of the road is commonly known as the East Trail, as it runs east-west across the state, in contrast to the road's otherwise distinctively north-south route. In Naples, Route 41 changes direction at an intersection, turning from west to north towards Tampa (or from south to east towards Miami).

As the Trail moves into Hillsborough County the historic communities of Ruskin, Florida and Gibsonton, Florida are south Hillsborough County high points. Ruskin was founded by the Commongood Society and Gibsonton populated by Carnival workers.

US 41 is in the process of being widened throughout the northern Tampa Bay suburbs. It is currently six lanes wide between Tampa, Lutz, and much of Land O' Lakes, and again between Garden Grove and Brooksville. It is also four lanes wide in Tampa south of BUS US 41, between a section north of Land O' Lakes, Masaryktown, and Garden Grove, and south of Inverness. A large portion of US 41 is co-designated along the unmarked Florida State Road 45 between Belle Meade and High Springs.

From US 92 in Tampa to US 41 Business and State Road 676 near the unincorporated Palm River-Clair Mel, US 41 carries the unsigned State Road 599 designation. It contains the northwestern end of the Tamiami Trail at the SR 60 intersection. It is normally three lanes wide, but between Interstate 4 and the northern terminus of SR 569 it is only two lanes wide. The unsigned state highway is 5.6 miles (9.0 km) long. At the northern terminus, US 41 turns west. (If one continues straight, 40th Street leads to Busch Gardens Tampa Bay.) Major intersections include State Road 574, SR 569, I-4, SR 60, and the Lee Roy Selmon Expressway (SR 618).

In Northern Florida, US 41 runs along the DeSoto Trail between Floral City and Williston and again between High Springs, and Lake City.

In Georgia, US 41 is paralleled by Interstate 75 all the way from Tennessee to Florida, and I-75 has largely supplanted US 41 as a major highway.

In Atlanta, Highway 41 was formerly carried on Spring Street near Five Points, but it has long been re-routed via Northside Drive around the downtown area. (It was a major truck route.) The Georgia Dome, Georgia World Congress Center and Philips Arena are located off Northside Drive. South of Atlanta, Metropolitan Parkway and Tara Boulevard carry the highway, along with its co-signed partner US 19, toward Griffin. North of Atlanta, the stretch of Highway 41 between Atlanta and Marietta was the first four-laned highway in Georgia when it was completed in 1938. Now, the Northside Parkway and the Cobb Parkway carry US 41 through northern Fulton and Cobb counties. This thoroughfare is the home of the Big Chicken, Cumberland Mall, the Cobb Galleria and the Six Flags White Water amusement park. US 41 also passes through the Georgia cities and towns of Dalton, Griffin, Macon, Warner Robins, Perry, Cordele, Tifton. US 41 has been rerouted to run along Inner Perimeter Road around Valdosta. US 41 Business runs through Valdosta. Valdosta is the last major stop before reaching Florida. The Atlanta Motor Speedway is located on US 19 and US 41 in Hampton. US 41 has been re-routed in Barnesville and been designated as a truck route and possible industrial area.

In Kentucky, US 41 runs from just north of the Ohio River to Guthrie, Kentucky in Todd County. There is a more than century-old border dispute between Indiana and Kentucky that is reflected by the route of US 41. This route is one of the few places where the Kentucky/Indiana border deviates from the Ohio River.

After crossing the Bi-State Vietnam Gold Star Bridges over the Ohio River, US 41 passes John James Audubon State Park, and passes through the city of Henderson. The route then crosses into Webster County, where it passes through the towns of Sebree and Slaughters. Next, it crosses into Hopkins County and passes through Hanson, Madisonville, Earlington, and Nortonville. It then goes into Christian County and through Trenton and Guthrie in Todd County.

In Madisonville US 41 branches off into a more Western route named US 41-A or Alternate 41 (only one of several alternate routes on US 41) that winds through Webster County, passing through Providence and Dixon before rejoining US 41 in Henderson.

In the state of Indiana, US 41 runs from the Ohio River south of Evansville to Chicago with US 12 and US 20 beneath the termini of the Chicago Skyway and the Indiana Toll Road. This is a distance of approximately 282 miles (615 km).

For its entire length north of Evansville, US 41 passes through largely rural portions of far western Indiana. It overlaps US US 150 and US 52 through some of these areas. US 41 is also the main north–south road through Terre Haute. However north of Terre Haute, US 41 becomes a secondary road, passing through smaller towns such as Rockville and Attica on the east side of the Wabash River. State Road 63 is the main route north of Terre Haute in this area since it is a four-lane highway on the west side of the Wabash River. US 41 returns to a four-lane divided highway just south of Boswell where SR 63 ends, staying as such until reaching Cedar Lake. From Cedar Lake north to the Illinois state line, US 41 is a well-travelled road with numerous stoplights, with the exception of the mile-stretch where it overlaps Interstate 80/94. Before leaving Indiana, US 41 travels through the city of Hammond where it is also known as Indianapolis Boulevard and Calumet Avenue. Hammond is the largest city traversed by US 41 between Evansville and Chicago.

US 41 enters Illinois cosigned with US 12 and US 20 on Indianapolis Boulevard beneath the Chicago Skyway. At the Illinois–Indiana state line, US 41 enters Chicago city limits. The three US routes run together for a few miles until US 12 and 20 separate from each other on the far south side. US 41 then runs along numerous small streets to Jackson Park, where US 41 turns north onto Lake Shore Drive, passing through Chicago's lakefront area as it runs along the western shore of Lake Michigan and past downtown Chicago.

On the north side of the city at Foster Avenue, US 41 separates from Lake Shore Drive. At Broadway, US 41 intersects the eastern terminus of US 14. US 41 continues along Lincoln Avenue in the northern part of the city, eventually meeting Skokie Boulevard, where US 41 turns north and parallels Interstate 94.

In the northern suburbs of Chicago, US 41 joins I-94 north for a short distance before splitting from the expressway and continuing north as the Skokie Highway for roughly 25 mi (40 km) to a point near the Wisconsin border. Just south of the border, US 41 rejoins I-94. The two co-signed routes continue northward into Wisconsin.

In Wisconsin, US 41 runs north and south along the eastern edge of the state. It enters from Illinois at Pleasant Prairie and is concurrent with Interstate 94 north to Milwaukee. From Milwaukee, it runs northwest to Fond du Lac and Oshkosh, then northeast to Appleton and Green Bay. The route is a major access point for Miller Park, home of the Milwaukee Brewers, the EAA AirVenture Oshkosh air show in Oshkosh, and for Lambeau Field, home of the Green Bay Packers. Beyond Green Bay, US 41 continues on to Oconto and Peshtigo before reaching the Michigan border at Marinette.

US 41 is a freeway for nearly 70% of its length through Wisconsin, with exceptions including a stretch in Milwaukee (Lisbon and Appleton avenues) and an expressway section north of Green Bay.

In the U.S. state of Michigan, US 41 is a state trunkline highway that enters the state via the Interstate Bridge between Marinette, Wisconsin and Menominee, Michigan. Along its 279.167-mile (449.276 km) route, US 41 serves as a major conduit for Michigan traffic. The route from the southern terminus to downtown Houghton is part of the National Highway System. The trunkline comprises mostly two lanes, undivided except for sections that are concurrent with US 2 near Escanaba or M-28 near Marquette. US 41/M-28 is a four-lane expressway along the "Marquette Bypass", and segments of the highway in Delta and Marquette counties have four lanes. and the Copper Country Trail National Scenic Byway. The trunkline ends at a cul-de-sac east of Fort Wilkins Historic State Park in Copper Harbor, serving the Central Upper Peninsula and Copper Country.

Along the route, US 41 passes through farm fields, forest lands, and along the Lake Superior shoreline. The highway is included in the Lake Superior Circle Tour and the Lake Michigan Circle Tour. It also passes through the Hiawatha National Forest and the Keweenaw National Historical Park. Historical landmarks along the trunkline include the Marquette Branch Prison, Peshekee River Bridge and the Quincy Mine.

When their routes were originally laid out in 1926, US 41's southern endpoint was in Naples, Florida, at the western endpoint of US 94, which ran east to Miami. In 1949, US 94 was decommissioned, and the entire route became part of US 41, giving it an east–west section that retained the hidden SR 90 designation. The former US 94 ended in Miami at the same intersection where US 41 (and SR 90) do now. In 1953, US 41 was extended along US 1 and State Road A1A (SR A1A) to terminate in Miami Beach, Florida, but it was truncated back to the earlier terminus in 2000. Prior to 1993, when the Florida Department of Transportation color-coded U.S. highways in Florida, the color used for US 41 was orange.

US 41 initially took a more westerly route between Nashville, Tennessee, and Hopkinsville, Kentucky. The current US 41 was US 241. In 1930, the two routes became US 41W and US 41E, but in 1943 the western route became US 41 Alternate, with the main US 41 moving to the east route.

In July 2005, efforts started in Congress to re-designate US 41 between Milwaukee and Green Bay, Wisconsin, as I-41. The new Interstate would also include US 45 between current US 41 and the intersection with I-94 and I-894. It is believed that US 41 at that time would then be re-routed to remain concurrent with I-41.