Kentucky Route 80 (KY 80) is a 464.936 mile (748.242 km) long state highway in southern Kentucky. The route originates on the state's western border at Columbus in Hickman County, and stretches across the southern portion of the state, terminating southeast of Elkhorn City on the border with Virginia. It is the longest Kentucky State Highway, though the official distance as listed in route logs is much less due to multiple concurrencies with U.S. Route 68 and U.S. Route 23.

The route was split into two segments from 2003 to November 2009. Construction and relocation of Kentucky 80 in Graves, Calloway and Marshall counties during this time caused the route to be split. A new, four-laned 8.5-mile section of Kentucky 80 opened in Calloway County on November 25, 2009. The route is now four-lanes from Mayfield to Aurora with plans to complete the four-laning from Aurora to Cadiz over the next few years.[citation needed]

From Columbus, the road passes through Hickman, Carlisle and Graves Counties to Mayfield. Before 2003, the road passed through Mayfield and into Marshall County before converging with U.S. Highway 68 in Aurora. The two-lane segment of former Highway 80 from Mayfield to Aurora now has two separate designations. From Mayfield to Brewers in Marshall County, the road retains its former co-designation as Kentucky Route 58. The segment from Brewers to Aurora is now designated as Kentucky Route 402.

From Mayfield, Kentucky 80 travels along a new four-lane corridor into Calloway County and on to Murray. The route continues through eastern Calloway County and into Marshall County before converging with U.S. Highway 68 near the eastern terminus of Kentucky 402 in Aurora.

From Aurora, it follows US 68 through Trigg, Christian, Todd, and Logan counties to Bowling Green (Warren County).

From Bowling Green to Somerset, Kentucky, Highway 80 is paralleled (and largely supplanted) by the Louis B. Nunn Cumberland Parkway, officially designated as the future route of Interstate 66. Highway 80 serves rural portions of Barren, Metcalfe (including the city of Edmonton), Adair, Russell, and Casey counties to Somerset (Pulaski County).

Between Somerset and London (Laurel County), Highway 80 is again the primary route. The state's Interstate 66 proposals call for Highway 80 to again be bypassed in this area, with the new road sharing only the crossing over the Rockcastle River gorge. This proposal has met with controversy, with area residents preferring that the new Interstate be built on the existing Highway 80 right of way.

From London to Hazard, Kentucky, Highway 80 is again supplanted, this time by the former Daniel Boone Parkway, renamed the Hal Rogers Parkway in 2003. Highway 80 serves rural portions of Clay, Leslie, and Perry counties before rejoining the Parkway near Hazard.

Highway 80 is a modern four-lane highway (though not controlled access) from Hazard through Knott County to Watergap, Kentucky in Floyd County where it converges with U.S. Highway 23. This section of Highway 80 was completely new construction, with the old highway's segments renamed with several designations, primarily Highway 550. Highway 80 continues with US 460 until reaching Belcher, Kentucky in Pike County and continues into Virginia from Elkhorn City as Virginia Highway 80.

Originally, westbound Route 80 continued via ferry across the Mississippi River to Belmont, Missouri, where it connected with Missouri Route 80, which travels west to U.S. Route 61/62 near Sikeston. That ferry has long since been discontinued.