Weatherford completed 21-of-35 passes, while Willie Reid had an 83-yard punt return for a touchdown to spark a string of 24 unanswered third-quarter points for the underdog Seminoles (8-4). Reid added 79 receiving yards on five catches and was selected the game's Most Valuable Player.
The Hokies (10-2) were held to 86 rushing yards on 31 attempts. Quarterback Marcus Vick threw for a career-best 335 yards with a score on 26-of-52 passing, but was sacked six times and picked off once.
Virginia Tech's Josh Morgan finished with 128 yards on seven grabs, including a 28-yard touchdown in the Hokies' fourth-quarter rally.
Virginia Tech entered the game ranked first in the country in scoring defense, total defense and pass defense.