Eddie Royal and Josh Morgan each had long touchdown catches for the Hokies (9-2, 5-2 Atlantic Coast Conference), who have won five straight games. They close the regular season next week against Virginia and are second in the Coastal Division to No. 18 Georgia Tech, which wrapped up the division title last week.
"I'm proud of this crowd," Virginia Tech coach Frank Beamer said. "And I'm proud of the way they play. They play hard. They keep battling. When you talk about Branden Ore going out, we overcame adversity as a football team."
Ore - who came in as the ACC's leading rusher at 109 yards per game - hurt his left ankle when he was tackled by Josh Gattis on a run that was wiped out due to a penalty midway through the first quarter. His leg folded awkwardly underneath him as he went down, and he was helped to the sideline, where he pounded his fist on a table while being examined by team officials.
He was eventually carted to the locker room. The school said he would be re-evaluated Sunday for what Beamer said was a high ankle sprain.
His teammates, however, kept the Hokies heading in the right direction.
It wasn't the kind of performance the Demon Deacons (9-2, 5-2) were hoping for in a nationally televised game. They can still clinch the conference's Atlantic Division title and a surprise appearance in the league championship game by winning at No. 21 Maryland next weekend.
But that fact provided little solace to coach Jim Grobe, whose team never led in its home finale. Facing the nation's top-ranked total defense, Wake Forest finished with 257 total yards - including just 62 yards rushing in a scheme that relies on its ability to move the chains on the ground. Travo Woods led Wake Forest's injury-depleted backfield with 35 yards.
That left almost all the pressure on Riley Skinner, who threw for 195 yards but couldn't lead the Demon Deacons into the end zone.
"When we can't run the football and they realize the only way you're going to move it is to throw it, you're not in very good position," Grobe said. "They really did to us what we wanted to do to them.
"We cannot go win at Maryland if we go and play like we did tonight."
The Hokies controlled the game the entire way, taking advantage of key missed tackles on both of their offensive touchdowns. On Virginia Tech's first possession, Glennon connected with Royal, who bounced off a hit from Kevin Patterson and raced in for a 49-yard touchdown about 3 1/2 minutes in.
The Hokies increased the lead on their first possession of the second half on a similar play. Glennon tossed a high pass to Morgan, who outjumped Riley Swanson and broke free from Gattis for a 53-yard score and a 14-3 lead with 11:58 left in the third.
They also got 74 yards rushing from Kenny Lewis Jr. in relief of Ore.
"With Branden going out, we knew we had to make some plays," said Glennon, who completed 14 of 21 passes for 252 yards. "I had confidence in myself and my teammates. And regardless of the situation and regardless of what Wake Forest was thinking, we were going to get the job done."
After the teams traded field goals, the Hokies' defense - which had allowed just 5.8 points per game in the previous four - came up with the clincher. Rouse knocked the ball loose from Harris on a screen pass, and Adibi scooped up a fumble and ran down the left sideline for a 24-6 lead with 3:01 left in the third quarter.
The Hokies' defense followed with a key stop of Rich Belton on a fourth-and-1 from the Virginia Tech 5-yard line early in the fourth to maintain that momentum.
"We can't do anything about what happened tonight," Skinner said. "It wasn't the performance we were hoping for. Give credit to Virginia Tech. ... They're fast, strong and they play smart football. They just outplayed us tonight."