Wilson, who carried the ball 16 times, scored on a 20-yard run less than a minute into the contest and later added scoring scampers of 19 and three yards for the Hokies (1-0).
Logan Thomas (9-of-19 passing, 149 yards) and Mark Leal (6-of-9, 113) each connected for a pair of scoring passes as Virginia Tech piled up 521 yards of total offense.
Marcus Davis hauled down scoring passes of 22 and 63 yards en route to 140 yards for the Hokies.
DeAndre Presley could manage only 89 yards on 7-of-18 passing for Appalachian State (0-1), while backup Jamal Jackson passed for a TD and ran for another in the loss.
2014: The Year in Music [PHOTOS]