Buchanan and Dickenson counties

Kentucky Route 80 runs alongside the Russell Fork from Millard to just shy of the Virginia state line. There it turns northeasterly along the west bank of Grassy Creek, which lies inside Virginia and forms the line between Buchanan and Dickenson Counties, in order to avoid the deep gorge through Breaks Interstate Park. Route 80 soon crosses into Virginia, and continues to parallel Grassy Creek until the split with Hunts Creek, where it (and the county line) turns southeast to follow that creek. About halfway to the community of Breaks, SR 80 crosses the creek and county line.

SR 80 passes the community of Breaks, leaving Hunts Creek there and running past the entrance to Breaks Interstate Park. It runs south through Camp Branch Gap, and then continues in a general southerly direction alongside small creeks and over two summits to State Route 83 east of Haysi. SR 80 and SR 83 overlap west alongside Russell Prater Creek into Haysi, where they meet State Route 63 at the point where Russell Prater Creek empties into the Russell Fork. The two routes turn south, but SR 83 soon splits to the west to follow the McClure River. SR 80 continues southeasterly along the Russell Fork past Martha Gap and Birchleaf to the point where the Russell Fork turns east; SR 80 continues next to Fryingpan Creek past Colley, then alongside Priest Fork to Sportsman Lake and through Abner Gap to the Abner Branch, rejoining the Russell Fork at Bee.

SR 80 and the Russell Fork continue past Davenport and Council. The fork ends as the road approaches Sandy Ridge and the Tennessee Valley Divide, which it climbs Big A Mountain via a series of hairpin curves.

Russell County

SR 80 descends from Big A Mountain into a relatively flat area, where it runs cross-country and next to small creeks via Honaker, the junction with State Route 67, and a bridge over the Clinch River at Blackford to U.S. Route 19 at Rosedale. There it turns southwest with US 19, alongside Elk Garden Creek, to Smithfield, where it splits to the south. SR 80 again runs cross-country past Rockdell, where it begins to climb Clinch Mountain, which it crosses (into Washington County) at Hayters Gap.

Washington County

SR 80 descends from Hayters Gap to the East Fork Wolf Creek. There it turns southwest, following the creek to the community of Hayters Gap, and then following Wolf Creek through a gap in Little Mountain to the North Fork Holston River at the community of River Bridge. It crosses the river and follows Logan Creek uphill to Lindell, where the land levels out. It continues to follow Logan Creek past Yellow Springs and Giesley Mill, then crossing a low summit to Meadow View. SR 80 crosses Interstate 81 at a Diamond interchange southeast of Meadowview, providing access on I-81, and then ends at U.S. Route 11 at Cedarville. State Route 803, formerly part of SR 80, continues southeast from Cedarville to Lodi.