U.S. Route 60 (US 60) in the Commonwealth of Virginia runs 303 miles (488 km) west to east through the central part of the state, generally close to and paralleling the Interstate 64 corridor, except for the crossing of the Blue Ridge Mountains, and in the South Hampton Roads area.

Between Lexington in the Shenandoah Valley and Richmond, I-64 uses a lower elevation crossing of the Blue Ridge Mountains located about 30 miles (48 km) further north, where it runs parallel to U.S. Route 250 through Rockfish Gap.

With the crossing of the Blue Ridge Mountains at Humphreys Gap at a higher altitude in more rugged terrain, US 60 in this area offers much more challenging and weather-sensitive driving conditions, as well as a history of many crashes in the years before I-64 was completed.

East of north–south U.S. Route 29 (which runs parallel to the eastern slope of the Blue Ridge), the older US 60 and I-64 gradually converge as they pass through the rolling hills of the rocky Piedmont region in an easterly direction to reach the Fall Line at Richmond, where they again become very close.

I-64 became part of the circumferential Hampton Roads Beltway and looping far south and west of Norfolk, rather than reaching the Atlantic Ocean.

Although older, Route 60 continues its west to east travel, becoming the public roadway actually closest to the waters of the Chesapeake Bay and the Atlantic Ocean terminating near the traditional resort strip at Virginia Beach.

Even that crossing, at Afton Mountain, can be very treacherous, and has been particularly notorious for accidents during reduced periods of visibility, motivating the state to install an innovative pavement lighting system.

A short distance east of Interstate 81, as it passes through Buena Vista, even before leaving the city limits, the roadway immediately begins a steep climb.

Continuing east, there is an additional shorter section of mountainous terrain before the road levels out somewhat into the rolling Piedmont region through the middle belt of the state.

Crossing into Chesterfield County, it intersects State Route 288, a semi-circumferential expressway around the southwestern quadrant of Metropolitan Richmond and becoming Midlothian Turnpike.

From this point east, the road becomes almost a continuous business district and widens to six lanes through the urban parts of Chesterfield County and the westernmost portion in the city of Richmond.

Midlothian was the site of coal mines after about 1700, with product transported overland to Manchester which was Richmond's sister city south of the river (until they merged in 1910).

This area was the scene of several major American Civil War battles during the Peninsula Campaign in 1862, and the roadway borders federal cemeteries at Government Road near the city limits and at Seven Pines.

Near Anderson's Corner at the junction of Virginia State Route 30 (near I-64 at exit 227), US 60 swings somewhat south to pass through Toano and Norge to reach Williamsburg, which I-64 bypasses slightly to the north.

These, with more lanes and higher speed limits, in combination with Warwick Boulevard, form the major east–west highways through modern-day Newport News.

A notable section of Huntington Avenue (the block between 25th and 26th streets) carries US 60 in both directions overlapping, and is possibly the only example of a highway in the United States with such a configuration.

Another project in Newport News to relocate and widen the portion of Route 60 west of Fort Eustis and construct a new crossing of Skiffe's Creek is in a planning stage.

US 60 continues as a 4-lane divided highway as it crosses over Lynnhaven Inlet on the Lesner Bridge and towards the First Landing State Park and Joint Expeditionary Base East at Cape Henry.

In 1802, Chesterfield County's coal manufacturers and residents petitioned the Virginia General Assembly for permission to construct a turnpike between the port of Manchester and Falling Creek.