U.S. Route 33 in West Virginia

US 33 crossing the Ohio River on the Ravenswood Bridge, viewed from Ravenswood, with the Ohio bank of the river in the distance

Seneca Rocks, along US 33 in Pendleton County, West Virginia (Wood engraving "The Cliffs of Seneca" by David H.Strother, published in 1872)

US 33 passes through Judy Gap (center), after descending the Allegheny Front (background; highest point is Spruce Knob)

View west along US 33 in Pendleton County

Shortly after entering West Virginia and crossing the Ohio River, US 33 turns south, then east in Ravenswood. It then joins SR 2's freeway, turning northeast, then east again to Silverton. The two routes then split, and US 33 joins Interstate 77 to Ripley. The route then turns east from I-77, joining US 119 at Spencer, then passing through extremely rural areas of Roane, Calhoun, Gilmer, and Lewis counties.

US 33 Intersects Interstate 79 at Weston, West Virginia. From Interstate 79 east, US 33 is a four-lane highway, part of Corridor H of the Appalachian Development Highway System. The four-lane segment continues on through rural areas of Upshur, and Randolph counties, to just a couple miles past Elkins.

At Harding, US 250 joins US 33 for several miles after Elkins, where US 33 joins SR 55 and returns to a two-lane road, except for a seven-mile (11 km) section of four-lane across Kelly Mountain between Canfield and Bowden. Passing through the Monongahela National Forest, US 33 crosses the Eastern Continental Divide between Harman and Onego at about 3,240 feet (990 m) elevation, entering Pendleton County, then descends the Allegheny Front along Seneca Creek, skirting the north end of Spruce Mountain, at 4,861 feet (1,482 m) the highest point of the Allegheny Mountains.

US 33 then joins SR 28 at Seneca Rocks, West Virginia, and continues south in the Potomac River headwaters through scenic forest and farmland landscapes. Turning eastward from SR 28 at Judy Gap, US 33 crosses North Fork Mountain at about 3,600 feet (1,100 m), with a turnout on the western slope offering a scenic view of the Germany Valley below and the more distant Allegheny Front from Spruce Knob to Dolly Sods. US 220 joins US 33 for about half a mile in Franklin. After Franklin, US 33 continues eastward through rural areas, then climbs steeply to cross Shenandoah Mountain at Dry River Gap at about 3,450 feet (1,050 m) into Rockingham County, Virginia.