The road begins at the interchange of SR 82-867. The road briefly overlaps SR 80 until it reaches southbound Fowler Street and northbound Park Avenue. Northbound and southbound BUS US 41 run parallel to each other until they reach the Edison Bridge where the two streets merge. After crossing over the Caloosahatchee River BUS 41 enters North Fort Myers where it briefly becomes a six-lane undivided highway only for the divider to return north of Cabanna Avenue. The road heads north, intersecting with State Road 78. Between State Road 78 and Powell Drive, the road becomes a four-lane divided highway and then a two-lane undivided highway north of Littleton Road. The road finally ends at a former wye at US 41.
U.S. Route 41 Business is an alternate route and former segment of U.S. Route 41 in Bradenton, Florida that begins at State Road 684 (Cortez Boulevard West) where it runs along 14th Street until it makes a sharp right turn onto 8th Avenue West and then makes another sharp left onto 9th Street West before intersecting with State Road 64 on eastbound 6th Avenue West and westbound Manatee Avenue West. The road continues north as it passes by the South Florida Museum before crossing the Green Bridge and moving onto 8th Street in Palmetto where it intersects 10th Street West, which leads to State Road 43 where the northern concurrency of U.S. Route 41 and U.S. Route 301. As 8th Street West passes by 21st Avenue West, it becomes Valencia Drive and curves to the northeast before terminating at an interchange with US 41 just south of the interchange between US 41 and US 19 in Memphis.
U.S. Route 541 was created in 1931 as a western alternate to US 41 between Palmetto and Tampa; US 41 then followed the present US 301 between those points. In 1938, US 41 was moved from Tampa north to Lutz, and the old route became an extension of US 541. US 541 was eliminated in 1951; the route north from Tampa became US 41 Business, while south from Tampa it became US 41, with old US 41 becoming an extension of US 301.
U.S. Route 41 in Valdosta has been rerouted to run on Inner Perimeter Road from its southern intersection with S. Patterson St. to its northern terminus with N. Valdosta St. U.S. Route 41 Business runs concurrently with Georgia State Route 7 Business from the intersection of Inner Perimeter Road and S. Patterson St. (which is just south of the Valdosta city limits) north along S. Patterson St. over the James Beck Overpass onto N. Ashley St. continuing north along N. Ashley St. where it rejoins U.S. Route 41 at the intersection of N. Valdosta St. and Innter Perimeter Rd.
U.S. Route 41 Business begins at the northern terminus of the US 41-129 overlap. Along the way, US 80 joins the overlap. When US 129 intersects Porter Street, BUS US 41 turns left and runs concurrent with Georgia Route 19 until it terminates at US 41 and Georgia Route 247.
U.S. Route 41A Bypass (US 41A Byp.) is a bypass of the city of Clarksville, Tennessee on its south side. It first splits off from the US 41A mainline at 2nd Street and Kraft, following Riverside Drive south along the Cumberland River, and then traveling concurrently with Tennessee State Route 76 past Tennessee State Route 13 and Tennessee State Route 48 where it begins bypass designation. The bypass travels to the east approximately 5 miles (8.0 km) along the edge of the Cumberland. Most of the road is a two-lane highway, occasionally widening to three lanes to accommodate truck traffic on hills. There is one light in the middle of the bypass, where Tennessee State Route 12 (Ashland City Highway) starts approximately 1.5 miles (2.4 km) before the bypass merges with US 41A (Madison Street) on the east side of Clarksville. From here, US 41A heads southeast to Nashville, Tennessee, where it merges with US 41.
Known and referred to locally as "U.S. 41-A" but signed as "Alternate U.S. 41," this route follows what was the original route of U.S. 41 between the cities of Madisonville and Henderson, Kentucky. It travels largely from east to west from its southern terminus at U.S. 41 on Madisonville's north side until reaching Kentucky Route 814 east of Providence. From that point, the road begins its turn toward the north, passing mostly through rural areas but also serving the small communities of Dixon and Poole.
US Highway 41 Business Route (BUS US 41) was a state trunkline highway that served as a business loop off US 41 in the US state of Michigan through the City of Marquette along Washington and Front streets. Jurisdiction over the two streets was transferred to the City as part of a route swap that resulted in the decommissioning of the trunkline. It was also previously co-designated BUS M-28, mirroring the BUS US 41/BUS M-28 designations along BUS M-28 in Ishpeming and Negaunee.
The U.S. Highway 41 Business Route serving Ishpeming and Negaunee is the only one of the three former business loops in Michigan that is still a state-maintained highway. it is no longer designated BUS US 41. US 41/M-28 was relocated to bypass the two cities' downtowns in 1937. The highway through downtown Ishpeming and Negaunee was redesignated US 41A/M-28A at the time  The Michigan State Highway Department later redesignated it ALT US 41/ALT M-28. Eventually it carried the BUS US 41/BUS M-28 designation before being designated BUS M-28 in 1958.
U.S. Highway 41 Business Route existed in Baraga in the early 1940s. As shown on the maps of the time, US 41 was relocated in Baraga between the publication of the December 1, 1939, and the April 15, 1940, MSHD maps. A business loop followed the old routing through downtown. The last map that shows the loop was published on July 1, 1941. BUS US 41 is shown under local control on the June 15, 1942, map.