U.S. Route 41 (US 41) is a United States Numbered Highway that runs from Miami, Florida, to Copper Harbor, Michigan. In Tennessee, the highway is paralleled by Interstate 24 all the way from Georgia to Kentucky, and I-24 has largely supplanted US-41 as a major highway, especially for large and heavy vehicles, such as tractor-trailer trucks and buses.

US 41, joined by US 76, enters Tennessee east of Interstate 75 on the outskirts of East Ridge. It is called "Ringgold Road" through East Ridge up to the Bachman Tunnel, where it enters Chattanooga. In Chattanooga, US 41 and US 76 becomes Westside Drive up to the intersection with Dodds Avenue, where for a short distance it is coexistent with Dodds Avenue. Then US 41 and US 76 becomes East Main Street in downtown Chattanooga up to the intersection with Broad Street (US 11 and US 64). At that point US 76 terminates, US 72 begins, and the now-conjoined US 41 and US 76 merges with US 11 and US 64, trekking southwestward around the base of Lookout Mountain into the Tiftonia community. Just west of Tiftonia, US 11 splits off, and it veers southwestward into Georgia. US 41, US 64, and US 72 take a westward path from Hamilton County into Marion County. US 41 breaks off from US 64 and US 72 at Jasper and joins with State Route 150 before climbing the mountains. US 41 leaves SR 150 and joins with SR 56 at Tracy City and runs southwest into Monteagle.

After reaching Monteagle, US 41, included as part of the older Dixie Highway, continues northwest into Pelham, in Grundy County, then runs closely parallel with I-24 into Coffee County, going through Hillsboro, Manchester (where the road is also named Hillsboro Blvd) and Beech Grove, before entering Rutherford County. From there, the highway continues diagonally through Murfreesboro (where the road is also named Broad St.), where the Dixie Highway joins up with US 70S. The Stones River National Battlefield is located very near US 41 and US 70S on the northwest side, standing as a monument of the Battle of Stones River which took place during the American Civil War. US 41/70S continues northwest through Smyrna, and LaVergne before reaching Davidson County. The road passes through Antioch, before reaching Nashville, where US 41 separates from US 70S. The road goes to south Nashville as Nolensville Pike or 31A 41A. US Route 41 goes through Nashville as Murfreesboro Rd, then Dickerson Pike, and comes out on the northeast side of the city joined with US 31W. US 41 continues northeast through Goodlettsville before breaking away from US 31W. US 41 then goes northwest and continues on into Robertson County, going through Springfield before heading west/northwest to the Kentucky border. Just before reaching Kentucky, US 41 briefly runs through Montgomery County.