Despite its short length, it is an important route connecting travelers from Ohio to the vicinity of Greater Pittsburgh via Weirton.

[7] Upon entering the state, US 22 parallels the Harmon Creek and reaches its first interchange with West Virginia Route 2 (WV 2) for Follansbee and Wheeling.

Continuing to parallel the Harmon Creek, US 22 passes to the east of Weirton with homes, neighborhoods, and mountainous hills dotting the west side of the road.

US 22 turns to an east direction before reaching a partial cloverleaf interchange (parclo) with CR 13 (Three Springs Drive) for the city center.

As of this day, the highway extended from a point 0.6 miles (0.97 km) west of Three Springs Drive to the Pennsylvania state line.

The bypass was located at a point roughly a mile (1.6 km) south of the previous routing which also entered Pennsylvania.

[14] On March 10, 1972, the final 1.4 miles (2.3 km) of US 22 were completed and opened to the public, connecting travelers from the Ohio to the Pennsylvania state lines.