US 250 enters Virginia on top of Allegheny Mountain, the ridgeline that forms the Virginia – West Virginia state line and the Eastern Continental Divide. The highway continues northwest into Pocahontas County, West Virginia toward Durbin and Elkins. US 250, which is known as Highland Turnpike, parallels the state line, then veers east and has a curvaceous descent along the east side of the mountain to the narrow valley of Back Creek. The highway climbs over Lantz Mountain before reaching Hightown in the Bluegrass Valley, which contains the headwaters of both the South Branch Potomac River on the north and the Jackson River, one of two chief tributaries of the James River, on the south. East of Hightown, US 250 crosses Monterey Mountain and enters the town of Monterey, the county seat of Highland County. The highway serves as the town's Main Street and intersects US 220 (Jackson River Road).