The northern terminus is at Interstate 77 exit 114 north of Pocatalico.

From its southern terminus, WV 622 proceeds northwest to Interstate 64, where WV 622 interchanges with the expressway by way of exit 47 on the southern edge of Cross Lanes.

The third lane terminates shortly after the intersection of Doc Bailey Road (Kanawha County Route 10.)

Outside of Cross Lanes, WV 622 proceeds eastward through Tyler Heights before resuming a northerly alignment at the northern terminus of West Virginia Route 501 east of town.

Roughly five miles to the northeast of WV 501, WV 622 intersects County Route 21, the former alignment of U.S. Route 21 through West Virginia.