WV 622 begins at WV 25 on the outskirts of Institute. 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. As the route turns 90 degrees to the northeast, WV 622 gains an extra turning lane, widening the road to three lanes as it enters 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. WV 622 turns north onto CR 21, running concurrent with the road for three miles (5 km) to I-77, where WV 622 comes to an end north of Pocatalico and six miles (10 km) north of the I-77/Interstate 79 junction. CR 21, however, continues northward from the interchange.
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