US 421 highlighted in red | |
| Route information | |
| Auxiliary route ofUS 21 | |
| Length | 941 mi (1,514 km) |
| Existed | 1930–present |
| Major junctions | |
| South end | |
| Major intersections |
|
| North end | |
| Location | |
| Country | United States |
| States | North Carolina,Tennessee,Virginia,Kentucky,Indiana |
| Highway system | |
U.S. Route 421 (alsoU.S. Highway 421,US 421) is a diagonal northwest–southeastUnited States Numbered Highway in the states ofNorth Carolina,Tennessee,Virginia,Kentucky, andIndiana. The highway runs for 941 miles (1,514 km) fromFort Fisher, North Carolina, toUS 20 inMichigan City, Indiana. Along its routing, US 421 serves several cities includingWilmington, North Carolina;Greensboro, North Carolina;Bristol, Tennessee andVirginia;Lexington, Kentucky; andIndianapolis, Indiana. US 421 is aspur route ofUS 21, which it meets west ofYadkinville, North Carolina.
| mi | km | |
|---|---|---|
| NC | 328 | 528 |
| TN | 43.4 | 69.8 |
| VA | 69.23 | 111.41 |
| KY | 272.4 | 438.4 |
| IN | 232.00 | 373.37 |
| Total | 941 | 1,514 |
US 421 begins atFort Fisher, North Carolina, and heads generally to the northwest toMichigan City, Indiana. Along the way, it passes throughBristol, Tennessee andVirginia;Lexington, Kentucky; andIndianapolis, Indiana.

US 421 begins nearFort Fisher State Recreation Area and heads through North Carolina's southeastern beaches toWilmington. It then heads in a northwesterly direction throughClinton,Dunn,Lillington,Sanford andSiler City to thePiedmont Triad region. Major highway junctions between north of Wilmington and Greensboro areNorth Carolina Highway 11 (NC 11),Interstate 95 (I-95),US 401,US 1,US 64 andI-85. In Greensboro, it follows theGreensboro Urban Loop paired with I-85 south of Greensboro, close to Pleasant Garden, andI-73 northwest of Greensboro, close to Colfax. It then departs the urban loop and connects toI-40 towardsForsyth County as it becomes its own freeway along the former Business Loop 40 alignment. Major intersections areNC 150,NC 66,NC 67,US 158 andUS 52 between Greensboro andWinston-Salem. After Winston-Salem, it intersects I-40 once again but continues westerly passing throughLewisville,Yadkinville,Wilkesboro andBoone. Major highway junctions between Winston-Salem and Boone areUS 601,I-77,NC 16,Blue Ridge Parkway,US 221 andUS 321. US 421 continues westerly into Tennessee towardsMountain City, Tennessee. US 421 is a limited-access freeway through Siler City northward. US 421 is a divided highway from north ofNC 49 all of the way toWilkesboro.

US 421 enters Tennessee from North Carolina atTrade. It is the oldest crossroads community in Tennessee and is the easternmost part of the state. The road "as the crow would fly" is a short distance in Volunteer State but traverses through two mountain ranges. After Trade, it ventures intoMountain City through a 40 mph (64 km/h) zone while bypassing the downtown area. After Mountain City, begins the two mountain ranges and in between them is the area ofShady Valley. The two ranges are a popular motorcycle route known as "The Snake". More than 400 curves over an approximately 30-mile (48 km) ride. After the second mountain range, it flattens out after theSouth Fork Holston River heading towardsBristol. US 421 enters Virginia on the Old Dominion side of Bristol. Major highway junctions between the NC and VA state lines areState Route 67 (SR 67) in Mountain City,SR 91 the new Mountain City bypass,SR-394, andUS 11E.
US 421 enters from Tennessee inBristol and goes west toWeber City,Duffield, andPennington Gap in Southwest Virginia. The route goes through the Cumberland and Powell Mountains, and goes byNatural Tunnel State Park near Duffield.
US 421 enters the Bluegrass State running 272.4 miles (438.4 km) from the Pennington Gap area in Virginia intoHarlan County.
For the distance between the Virginia state line and closer toHal Rogers Parkway, it is a major north–south two-lane highway. However, its passing zones are largely limited to a stretch after the Virginia line, through Harlan and alongUS 119. US 421 then crosses Pine Mountain and entersLeslie County, turning west atHyden and paralleling the Hal Rogers Parkway. BetweenManchester andMcKee, US 421 functions as more of a local road with many curves.
The roadway improves as it descends from the Cumberland Plateau into the Bluegrass Region at Big Hill inMadison County nearBerea. It joinsUS 25 at the Blue Grass Army Depot south ofRichmond and roughly parallelsI-75 towardsLexington. Through Lexington, it is Richmond Road, Main Street and Leestown Road. The segment between Lexington and Frankfort was once designatedKentucky Route 50 (KY 50).US 62 runs briefly with US 421 in this section.
InFrankfort, US 421 runs with US 60 on the west side of town, then runs within the city's northern bypass, briefly joiningUS 127. US 421 then traverses the very hilly area of northwestFranklin County, around theFlag Fork community. It then runs throughHenry andTrimble counties, exiting the state atMilton, crossing theOhio River intoMadison, Indiana via theMilton–Madison Bridge.

US 421 winds through the southern part of Indiana as it runs from Madison, in the southeastern part of the state, toIndianapolis. North ofGreensburg, US 421 intersects and merges withI-74 west, through theShelbyville area en route to Indianapolis. Originally, US 421 followed Southeastern Avenue into downtown Indianapolis, where it merged with US 40 (Washington Street) to West Street, then turned north, following West Street, Northwestern Avenue (later MLK Street), and Michigan Road up to the northwest side of the city. US 421 went past the Pyramids, an Indianapolis landmark. North ofIndianapolis, US 421 continues to the north-northwest, providing a direct highway link between Indianapolis andMichigan City. US 421 ends at its junction withUS 20 on the south side of Michigan City. Originally, the highway's end was a few miles north at the junction withUS 12 near the shores of Lake Michigan.
US 421 mainly followed the same route between Clinton and Wilmington. However, there are several old alignments from Clinton to the Tennessee state line.
US 421 is projected to be upgraded to a freeway in Indiana from Greensburg to Versailles. US 421 freeway will go near, or pass throughNapoleon andOsgood.[citation needed]

