U.S. Route 45 is a major north-south United States highway and a border-to-border route, from Lake Superior to the Gulf of Mexico. A sign at the highway's northern terminus notes the total distance as 1,297 miles (2,087 km).
U.S. Route 79 is a United States highway in the Southern United States. The route is officially considered and labeled as a north–south highway, but its path is actually more of a diagonal northeast–southwest highway. The highway's northern/eastern terminus is in Russellville, Kentucky, at an intersection with U.S. Route 68 and KY 80. Its southern/western terminus is in Round Rock, Texas, at an interchange with Interstate 35, ten miles (16 km) north of Austin. US 79, US 68, and Interstate 24/US 62 are the primary east–west access points for the Land Between the Lakes recreation area straddling the Kentucky/Tennessee border.
U.S. Route 25 or U.S. Highway 25 (US 25) is a north–south United States Numbered Highway that runs for 750 miles (1,210 km) in the Southern and Midwestern U.S. Its southern terminus is in Brunswick, Georgia, from where it proceeds mostly due north, passing through the cities of Augusta, Georgia; Greenville, South Carolina; and Asheville, North Carolina, before dividing into two branches, known as US 25W and US 25E between Newport, Tennessee, and North Corbin, Kentucky. After passing through Richmond and Lexington, Kentucky, it reaches its northern terminus at Ohio state line in Covington, Kentucky. The route is an important crossing of the Appalachian Mountains, and it is covered by three of the corridors of the Appalachian Development Highway System (ADHS). When the highway was originally established in 1926, the route extended from North Augusta, South Carolina, to Port Huron, Michigan. The southern end was extended to its current terminus in 1936, while the northern end was truncated in 1974.
U.S. Route 421 is a diagonal northwest–southeast United States Numbered Highway in the states of North Carolina, Tennessee, Virginia, Kentucky, and Indiana. The highway runs for 941 miles (1,514 km) from Fort Fisher, North Carolina, to US 20 in Michigan City, Indiana. Along its routing, US 421 serves several cities including Wilmington, North Carolina; Greensboro, North Carolina; Bristol, Tennessee and Virginia; Lexington, Kentucky; and Indianapolis, Indiana. US 421 is a spur route of US 21, which it meets west of Yadkinville, North Carolina.
U.S. Route 641 (US 641) is a U.S. Route in Tennessee and Kentucky. It runs for 165.45 miles (266.27 km) from US 64 south of Clifton, Tennessee to an intersection with US 60 in Marion, Kentucky. While it is considered a spur route of U.S. Route 41, the two routes no longer connect.
U.S. Route 31E (US 31E) is the eastern parallel route for U.S. Highway 31 from Nashville, Tennessee, to Louisville, Kentucky.
State Route 254 is a west–east state highway in Davidson County, Tennessee. For the majority of its length, it forms part of Old Hickory Boulevard, with the rest known as Bell Road.
U.S. Route 79 in Tennessee enters the state from Arkansas via the Memphis & Arkansas Bridge in Memphis, and runs northeast through western and the northwestern portions of middle Tennessee, and leaving the state into Kentucky northeast of Clarksville. Along the route, US 79 is accompanied with several concurrencies, including hidden designations, throughout its alignment in Tennessee.
Kentucky Route 66 is a 46.59-mile-long (74.98 km) state highway in southeastern Kentucky. The route runs from Oneida in Clay County to Pineville in Bell County.
U.S. Route 231 in Kentucky runs 86.465 miles (139.152 km) from the Tennessee state line near Adolphus to the William H. Natcher Bridge on the Ohio River near Rockport, Indiana. It crosses the state mainly in the west-central region, traversing Allen, Warren, Butler, Ohio, and Daviess Counties.
U.S. Route 127 (US 127) in Kentucky runs 207.7 miles (334.3 km) from the Tennessee state line in rural Clinton County to the Ohio state line in Cincinnati. The southern portion of the route is mostly rural, winding through various small towns along the way. It later runs through the state capital of Frankfort before continuing north, eventually passing through several Cincinnati suburbs in Northern Kentucky, joining US 42 near Warsaw and US 25 in Florence before crossing the Ohio River via the Clay Wade Bailey Bridge.
Pruden is an unincorporated community located partly in Bell County, Kentucky and partly in Claiborne County, Tennessee, in the southeastern United States. It is located along Tennessee State Route 90 and Kentucky Route 74, which intersect at the state line, in the upper Clearfork Valley.
State Route 90 is a 13.5-mile-long (21.7 km) state highway in Campbell and Claiborne counties in the U.S. state of Tennessee. It serves the communities of Morley, White Oak, Eagan and Clairfield in Tennessee, and Pruden at the Tennessee-Kentucky state line.
Kentucky Route 94 is a 79.816-mile-long (128.451 km) state highway in Kentucky that runs from Tennessee State Route 78 at the Tennessee state line to KY 80 southwest of the unincorporated community of Aurora via Hickman, Water Valley, and Murray.
Kentucky Route 97 is a 18.262-mile-long (29.390 km) state highway in Graves County, Kentucky that runs from Tennessee State Route 69 and State Line Road West on the Kentucky-Tennessee state border southeast of Sedalia to KY 80, KY 121, and KY 121 Business just southeast of Mayfield.
Kentucky Route 190 (KY 190) is a 21.5-mile-long (34.6 km) state highway in the U.S. state of Kentucky. The highway travels through rural areas of Bell County.
Kentucky Route 186 (KY 186) is a 3.0-mile-long (4.8 km) state highway in the U.S. state of Kentucky. The highway connects mostly rural areas of Bell County with Middlesboro.
Kentucky Route 441 (KY 441) is a 4.897-mile-long (7.881 km) state highway in the U.S. state of Kentucky. The highway travels through mostly urban areas of Bell County. Virtually the entire highway is within the city limits of Middlesboro.
SR 90 at the Tennessee state line in Pruden 
US 25E in Middlesboro 
