Corridor D begins at the western edge of the Appalachian Regional Commission area at the Hamilton County–Clermont County border east of Cincinnati.

The highway crosses the Ohio River on the Blennerhassett Island Bridge just west of Belpre.

Corridor D crosses the Little Kanawha River and interchanges with Interstate 77 near Parkersburg shortly after entering West Virginia.

In Clarksburg, it crosses the West Fork River and ends at the Interstate 79 interchange, with U.S. Route 50 continuing eastward as a two-lane mountain road.

The earliest segment of Corridor D, or US 50, to open in West Virginia was a six-mile (10 km) segment in 1967 [1] from an isolated point near Sherwood in Doddridge County (MP 15) to WV 23 in Salem in Harrison County (MP 1.52).

Two years later, a segment from Salem east to CR 11 at Wolf Summit (MP 7) opened to traffic.

Construction began in 2000 with the start of the Godbey Fields complex in Parkersburg, West Virginia.

[11] This 1.32-mile (2.12 km) four-lane divided freeway is the final roadway section of the corridor from Clarksburg and Cincinnati without the Ohio River crossing.

The last Corridor D project, the Blennerhasset Bridge crossing the Ohio River, was opened on June 13, 2008.