U.S. Route 58 is an east–west U.S. Highway that runs for 508 miles (818 km) from U.S. Route 25E just northwest of Harrogate, Tennessee, to U.S. Route 60 in Virginia Beach, Virginia. Until 1996, when the Cumberland Gap Tunnel opened, US 58 ran only inside the commonwealth of Virginia. It was then extended southwest along a short piece of former US 25E, which no longer enters Virginia, to end at the new alignment in Tennessee. For most of its alignment, it closely parallels Virginia's southern border with North Carolina.

U.S. Route 25E (US 25E) is the eastern branch of US 25 from Newport, Tennessee, where US 25 splits into US 25E and US 25W, to North Corbin, Kentucky, where the two highways rejoin. The highway, however, continues as US 25E for roughly two miles (3.2 km) until it joins Interstate 75 (I-75) in the Laurel County community of North Corbin at exit 29. The highway serves the Appalachia regions of Kentucky's Cumberland Plateau and the Ridge-and-Valley section of East Tennessee, including the urbanized areas of Corbin and Middlesboro in Kentucky and Morristown in Tennessee.