The visiting Beavers, who came into the game 2-0 on the season after beating Pacific and Boise State, jumped out to a quick 10-0 first quarter lead on the Cardinals.
But the Cardinals took the Beavers punch, got back on their feet, then delivered a powerful blow of their own, scoring the games next 42 points.
After Oregon kicker Alex Serna's 43 yard field goal put the Beavers ahead 10-0 with 2:23 left in the first quarter, Louisville quarterback Brian Brohm connected with wide receiver Harry Douglas for a 46 yard gain to set up Brohm's 4 yard touchdown pass to tight end Gary Barnidge.
The Louisville defense held Oregon State
receiver Matt Hass in check most of the game.
"I thought our defense really got us going," Louisville coach Bobby Petrino said. "Once we started hitting the quarterback, we got some turnovers and big plays."
"I was very proud of our team after we got behind," he added. "I like to run the ball, but they were bringing nine guys to the line to stop it so we had to open it up. They play a really unique defense that hurts you in the run game."
The Cardinals then went almost 8 minutes without a score, before busting loose for three touchdowns in the final 5:16 of the first half. Bush scored from 6 yard out to put U of L ahead 21-10 with 5:16 left before intermission, while Mario Urrutia and Joshua Tinch both caught touchdowns passes from Brohm for a 35-10 lead at the break.
Urrutia, a redshirt freshman, saw his first extentive action of the season and made the most of it, catching a career-high 7 passes for 175 yards (10th most ever by a U of L receiver) and two touchdowns (22 yards, 69).
"Mario made play after play," Petrino said. "He's 6-6, 220-poundand he's very fast and has great hands."
After the break, it was all Louisville. The Cardinals defense harrassed Oregon Quarterback Matt Moore the entire game, building a 56-13 lead when Urrutia caught a 68 yard strike from Brohm.
The U of L special teams and defense also came up with several big plays. Linebacker Brandon Johnson blocked a punt and returned a Moore interception 15 yards for a touchdown in the third quarter. Defensively, U of L has held their first two opponents to a combined 89 yards rushing (52 total attempts; UK 47, OSU 42).
The Beavers' also didn't have an answer for Elvis Dumervil, who broke Pat Swilling's (Georgia Tech) NCAA record for the most sacks (8) in two straight games. Dumervil, who had six sacks in the season-opener against Kentucky, recorded three more sacks against the Beavers.
The Louisville offense was in high gear after gaining just 388 yards against Kentucky. The Cardinals gained 553 yards on 50 plays, an outstanding 11.1 yard average per play.
Brohm completed 18-21 (81 percent) passes for 368 yards and five touchdowns with one interception. Running back Michael Bush carried 11 times for 57 yards and two touchdowns.
Sophomore wide receiver Harry Douglas also had a big day, catching three passes for 91 yards, including a 34 yard touchdown reception from Brohm. Backup quarterback Hunter Cantwell completed all three of his passes, including a yard touchdown strike to Montrell Jones late in the second half.
Oregon State's star receiver, Matt Hass, was contained most of the game by Louisville's secondary, though he did make nine catches for 163 yards. Quarterback Matt Moore completed 25-48 passes for 317 yards and one touchdown.
42,647 fans watched the Cardinals improve to 11-1 at PJCS under Petrino.
Louisville will travel to South Florida next week for both teams Big East Conference opener.