West got the starting nod for the Atlantic Coast Conference-member Deacons (3-8) when Phil Barnhill, Wake Forest's fifth all-time passing yardage leader, injured an ankle late in the week during practice.
West completed 15 of 28 passes for 229 yards and connected on touchdown pass plays of 45 and 12 yards to Todd Dixon and 37 yards to Walter Rasby.
The Commodores (1-9), members of the Southeastern Conference, saw their losing streak extended to seven games.
Vanderbilt took a 7-0 lead on a 34-yard run by Corey Harris with 6:23 left in the first quarter.
But West took Wake Forest to the Commodore end zone on four of the Deacons' next five possessions.
Wake Forest tied the score, 7-7, with 3:44 left in the first quarter when West connected with Dixon at the Vanderbilt eight-yard line and Dixon sidestepped a Commodore defender and ran into the end zone to complete a 45-yard scoring play.
The Demon Deacons moved 80 yards on their first possession of the second quarter with Williams sweeping his own right end for a 10-yard touchdown run and a 14-7 Wake Forest lead.
Tony Rogers scored on a four-yard run late in the quarter to give Wake Forest a 21-7 lead.