| State: | KY |
| Type: | US |
| Route: | 421 |
| Maint: | KYTC |
| Map Custom: | yes |
| Map Notes: | US 421 highlighted in red |
| Length Mi: | 250.536 |
| Length Round: | 3 |
| Length Ref: | [1] |
| Direction A: | South |
| Terminus A: | at the Virginia state line near Pennington Gap, VA |
| Direction B: | North |
| Terminus B: | at the Indiana state line near Madison |
| Counties: | Harlan, Leslie, Clay, Jackson, Rockcastle, Madison, Fayette, Scott, Woodford, Franklin, Shelby, Henry, Trimble |
| Previous Type: | KY |
| Previous Route: | 420 |
| Next Type: | KY |
| Next Route: | 422 |
U.S. Route 421 (US 421) in the U.S. state of Kentucky is a 250.536adj=midNaNadj=mid north–south United States highway that traverses twelve counties in the central and eastern parts of the state. It travels in a southeast-to-northwest path from the Virginia state line near Pennington Gap to the Indiana state line, on the Ohio River at Milton, Kentucky and Madison, Indiana.[2]
US 421 enters Harlan County from Lee County, Virginia, and meets US 119 near Harlan. At Hyden, US 421 turns westward towards Clay County, and crosses the Hal Rogers Parkway via an overpass without access near Manchester.[3]
At Manchester, US 421 turns northwestward towards Jackson County, through McKee. It traverses the far northeastern corner of Rockcastle County before entering Madison County where it joins U.S. 25 south of Richmond near the Blue Grass Army Depot. US 25 and US 421 runs concurrently through Richmond, and all the way to the I-75 junction.[4]
US 25/421 also runs concurrently with I-75 between Exits 97 and 99. After Exit 99, the two U.S. routes continue to run concurrently until downtown Lexington just after crossing US 27/60/68. While US 25 makes a right turn onto Georgetown Road, US 421 continues straight northwestward, as Leestown Pike, towards Midway and Frankfort.[5]
In Frankfort, US 421 has concurrencies with US 60 on the east side of town, and US 127 on the north side. US 421 continues northwestward into Henry and far northern Shelby counties before crossing the Exit 34 exit of I-71. US 42 in Bedford is the last major intersection in Kentucky before US 421 crosses the Ohio River from Trimble County into Jefferson County, Indiana.[6]
| State: | KY |
| Type: | KY |
| Route: | 50 |
| Location: | Frankfort-Lexington, Kentucky |
| Formed: | 1929 |
| Decommissioned: | 1952? |
| Length Mi: | 20.5 |
US 421 did not have any presence in Kentucky until it was extended into Kentucky and Indiana at one point between 1939 and 1957, probably in the late 1940s or early 1950s.[7] When US 421 was designated into Kentucky, it was routed onto the following existing routes: