Vick, who was 11-of-21 for 205 yards, threw a five-yard touchdown pass to Jeff King late in the game, as the 12th-ranked Hokies (11-2) came on strong against No. 15 Louisville in the final period.
Trailing 24-21 late in the game, Vick's five- yard scoring strike to King gave Virginia Tech a 28-24 edge.
Cedric Humes ran for 111 yards and a TD on 22 carries for Virginia Tech.
Hunter Cantwell threw three touchdown passes for Louisville (9-3), which had its five-game winning streak end. The Cardinals were appearing in their eighth straight bowl game and 13th overall.
Louisville's Michael Bush had 93 yards rushing on 16 touches.