The route travels northeast as a four lane divided highway, through a small section of Cumberland Gap with a few businesses.

Past Gibson Station, the highway passes northeast through an area of a rolling hills with homes surrounding either side of the road.

It is paralleled by Indian Creek on its southeast side, with the route crossing over its Pendleton Branch, prior to intersecting SR 691 in the village of Wheeler.

US 58 continues northeast from Wheeler, before turning due east again while passing along the southern edge of the Wilderness Road State Park.

The route crosses Indian Creek twice, before intersecting SR 684 to the southwest of a park and ride lot, and the DeBusk Veterinary Teaching Center of Lincoln Memorial University.

The route then dips south through more rural areas of rolling hills, residences, and farmland before turning northeast once more.

After passing through some hill cuts with stone sides and crossing over the Roaring Branch of Indian Creek, US 58 reaches the unincorporated town of Ewing.

US 58 continues northeast through more rural forests and farmland along the southeastern slope of Poor Valley Ridge, before reaching the unincorporated town of Rose Hill.

Here US 58 crosses over Burning Well Road, Hardy Creek, and the railroad line of CSX Transportation (former L&N) leading to the Hagan's Switchback, on a twin-span beam bridge.

US 58 then makes a curve to the southeast through hilly wooded areas, before crossing over Dry Creek and meeting State Routes 880 and 758 at an intersection.

The two routes stay concurrent until I-81 exit 19 in Abingdon, where US 58 resumes its eastward journey close to the Virginia–North Carolina state line.

Continuing eastward, the route crosses the Blue Ridge Parkway in the unincorporated community of Meadows of Dan before winding its way to Martinsville, where US 58 and US 220 share a southern bypass of the city.

Drivers continuing into the city without exiting onto US 58 east instantly enter Virginia before going under the bridge that carries the bypass.

), splits from the main route in Abingdon, Virginia and travels northwest (signed west) as the "Trail of the Lonesome Pine" to Coeburn.