Knight, a redshirt freshman, rushed for 103 yards on 13 carries and threw three touchdown passes - two to Jalen Saunders - and No. 16 Oklahoma beat the Warhawks 34-0 on Saturday night.
Oklahoma gave coach Bob Stoops his 150th career win, putting him seven behind Barry Switzer on the Sooners' career coaching wins list. Oklahoma is 5-0 under Stoops in August games and 14-1 in home openers, having lost only to Texas Christian in 2005.
Knight became the first Oklahoma quarterback to rush for 100 or more yards in a game since Jason White had 117 yards rushing against Kansas on Oct. 13, 2001.
"The first game, you come out and you hope everything goes well," Knight said. "We struggled a little bit early but just got comfortable as the game went on and made some big plays. The guys up front did a hell of a job . and we got it going.
"I felt good. From the beginning . I was dealing. I just missed a few things here and there. Nothing big. We know we can correct it this week. That's the good thing about this game, is we know we can only go up from here."
Louisiana-Monroe upset then-No. 8 Arkansas on the road to open the 2012 season, but the Warhawks didn't get untracked offensively against a revamped Oklahoma defense. The Warhawks crossed midfield only twice and recorded only nine first downs and 166 yards of offense.
"They took it to us and we didn't respond very well," Louisiana-Monroe coach Todd Berry said. "We knew that we were facing a great football team, a well-coached football team. But, quite honestly, I thought we had a chance coming in, based off of past history and all other kinds of things."
Knight, a redshirt freshman, was the fourth freshman quarterback to start a season for Oklahoma in modern times, joining Steve Collins (1989), Eric Moore (1995) and Sam Bradford (2007).
Unlike Bradford - who wowed fans in his debut against North Texas - Knight didn't produce a first-game passing highlight reel, particularly in the first half, when he consistently overthrew or underthrew receivers on swing passes and went 7 of 21 for 42 yards. He had three throws batted down at the line of scrimmage and nearly had a pass intercepted in the end zone.
Knight threw the football considerably better as the game progressed and finished 11-of-28 passing for 86 yards with one interception. He also showed off his mobility - which helped him beat out junior Blake Bell for the starting job - while leading the Sooners in rushing.
"You saw his ability to run and the opportunities it gives you," Oklahoma coach Bob Stoops said. "I'm sure he'll settle down and get smoother with some of his throws."
Oklahoma rushed for 305 yards, with tailbacks Damien Williams, Brennan Clay and Roy Finch contributing 66, 43 and 42 yards, respectively.
Oklahoma managed only one first down on its first four possessions, on a 24-yard scramble by Knight on the game's third play. The Sooners decided to go to the ground on their fifth possession, with good results. On the 14-play, 78-yard march, they ran 11 times before Knight capped the drive by checking off a play at the line of scrimmage, then hitting Saunders on a 12-yard scoring pass.
Two other run-heavy drives set up second-quarter field goals of 41 and 33 yards by Michael Hunnicutt.
Meanwhile, Oklahoma's defense - which closed the 2012 season with three atrocious performances in the Sooners' final four games - shut down Louisiana-Monroe's multiple-look offense. The Sooners turned quarterback Kolton Browning, the Sun Belt Conference preseason offensive player of the year, into a one-dimensional player by limiting his running opportunities.
Browning, who led the Warhawks in rushing last season, had 3 yards on four carries and completed 20-of-39 passes for 128 yards. He said after the game he was limited by a leg injury.
"I was trying to scramble one time and my leg just wasn't quite cooperating with me," he said. "I didn't get the burst I wanted to get running away from them."
The Warhawks reached the Oklahoma 23 midway through the first quarter, but an offensive pass interference penalty took them out of scoring range. Louisiana-Monroe didn't cross midfield again until two minutes into the fourth quarter.
"Defensively, it's one of the better games we've had in a long, long time," Stoops said. "All the assignments, the communication, was maybe as sharp as we've had."
Knight threw an 18-yard scoring pass to Saunders to make it 27-0 after Louisiana-Monroe's Justin Manton was stopped short of a first down on a fake punt. Saunders returned a punt 45 yards to the Louisiana-Monroe 20 to set up a 13-yard touchdown pass from Knight to Trey Metoyer with 38 seconds left in the third quarter to put the Sooners up 34-0.
Bell entered the game for Oklahoma with 10:53 left and finished the game for the Sooners.
The Sooners are 35-2 in nonconference home games with Stoops at the helm. Besides TCU in 2005, Notre Dame won last season at Gaylord Family-Oklahoma Memorial Stadium.