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.
Notable deaths of 2014 [PHOTOS]
Michael Sam cut from the Dallas Cowboys