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.

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.

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.