It is a popular alternative to Interstate 64 (I-64) when going from Richmond and other points in central Virginia to the Currituck Sound and Outer Banks of North Carolina, avoiding the congestion and tunnels of the more northerly I-64 corridor.

The U.S. Highway heads southeast as a two-lane road parallel to Norfolk Southern Railway's Buchanan Branch in the narrow valley of the Levisa Fork of the Big Sandy River.

US 460 re-enters Virginia at the town of Glen Lyn in Giles County at the northwestern end of the New River Valley region.

The new interchange is just south (east) of the current intersection and serves both the Virginia Tech campus and the Corporate Research Center via new roads and a relocated Southgate Drive (including two roundabouts).

At the southern edge of the research park, US 460 meets its business route (Main Street) at a complex interchange featuring many flyover ramps and a variety of direct and indirect connections to allow every movement between the two highways.

The two directions of US 460 continue along the collector-distributor lanes of I-81 east to the Interstate's partial cloverleaf interchange with US 11 and the eastern end of US 460 Bus., where US 460 exits into a concurrency with US 11.

At the bottom of the descent, US 460 and US 11 expand to a four-lane divided highway and parallel the Christiansburg District rail line and Spring Branch to the stream's confluence with the South Fork of the Roanoke River at Shawsville.

The highways intersect SR 112 (Wildwood Road), a connector with I-81, then pass the historic Preston House and veer away from the railroad and river west of their junction with US 11 Alt.

US 460 continues east past the Williams-Brown House and Store, Salem Presbyterian Parsonage, and Longwood Park and the western end of Lynchburg Turnpike.

US 460 and US 221 gradually curve east as Lynchburg Salem Turnpike, parallel the South Folk of Goose Creek, and pass through the communities of Villamont and Montvale, between which the U.S.

(Blue Ridge Avenue), which parallels the railroad toward downtown Bedford, where it intersects SR 43; the interchange has no direct access from the westbound business route to the eastbound U.S.

Immediately to the north of the junction, US 460 and US 29 cross over Norfolk Southern's Danville District rail line and enter the independent city of Lynchburg.

The three U.S. Highway continue northeast across Norfolk Southern's Durham District rail line to the end of the freeway at a partial cloverleaf interchange with Campbell Avenue, which carries US 501 southeast toward Rustburg and US 460 Bus.

US 460 and US 29 continue along four-lane divided Richmond Highway, which heads east past Falwell Airport and across Norfolk Southern's Blue Ridge District.

US 460 and SR 24 continue east parallel to the Blue Ridge District rail line through Spout Spring to the town of Appomattox.

(Confederate Boulevard) splits south toward the center of town at a diamond interchange that also marks the southern terminus of SR 26 (Oakville Road).

serving Pamplin City, which provides access to SR 47, splits southeast along the road while US 460 curves east and enters Prince Edward County.

US 460 continues east parallel to Norfolk Southern's Blue Ridge District into the town of Crewe, where the highway follows Virginia Avenue.

The U.S. Highway passes through the hamlets of Wilsons, Hebron (where it crosses to the south side of the railroad), Ford, Walkers, Church Road, and Sutherland as it approaches Petersburg.

The highways have a diamond interchange with Squirrel Level Road then cross over CSX's North End Subdivision and pass under US 301 Alt.

The U.S. Highway becomes undivided and parallels the rail line through New Bohemia and Disputanta on either side of its intersection with SR 156 (Prince George Drive).

East of Windsor, US 460 veers away from the Norfolk Southern rail line and enters the independent city of Suffolk as Pruden Boulevard.

US 460, US 13, and US 58 head east from Suffolk along six-lane divided Military Highway parallel to CSX's Portsmouth Subdivision rail line across the northern fringe of the Great Dismal Swamp.

The highways curve southeast and cross over an old railroad grade, then veer back east and meet I-64 (Hampton Roads Beltway) at a diamond interchange.

US 460 and SR 166 follow a two-lane road with center turn lane under I-464 (Martin Luther King Jr. Memorial Highway) and across Milldam Creek.

Immediately to the north of the interchange, the highways pass under Hampton Roads Transit's Tide Light Rail and its elevated NSU station at the southwest corner of the Norfolk State University campus.

[11] In the early 1970s, the former Virginian Railway right-of-way along the north bank of the New River eastward from a point near the Virginia-West Virginia border, near Glen Lyn to Narrows (both in Virginia) was acquired by VDOT's predecessor agency from the Norfolk and Western Railway to enable four-laning of the highway through the narrow space between the river and rocky bluffs.

[citation needed] As they continued west, they reached a station in Prince George County where they could not agree on a suitable name from the books.

William Mahone became a Major General in the Confederate Army during the American Civil War, and later, a Senator in the United States Congress.

In modern times, a large portion of U.S. Highway 460 between Petersburg and Suffolk is named General Mahone Boulevard in his honor.