Teddy Bridgewater threw his hands up in disbelief after throwing an interception in the second quarter.
With the way Bridgewater played Sunday, it's no wonder the junior quarterback was dumbfounded.
Bridgewater, one of the preseason favorites to take home the Heisman Trophy, picked apart Ohio's defense to the tune of 355 passing yards and a career-high tying five touchdowns as No. 9 Louisville rolled over the Bobcats, 49-7, in the season opener for both programs.
"It was just fun to watch Teddy. It's amazing how he continues to develop and just gets better and better," Louisville head coach Charlie Strong said.
Auburn transfer Michael Dyer ran for a 46-yard touchdown while Damian Copeland and Kai De La Cruz hauled in two scores apiece for the Cardinals (1-0), who will play in the American Athletic Conference this season prior to joining the Atlantic Coast Conference.
Louisville's defense, a unit that brought back a slew of starters from last year's Sugar Bowl-winning team, held Ohio to 273 yards and just 13 first downs, most coming with the outcome already decided.
The Bobcats (0-1) were unable to duplicate last year's run of seven straight wins to begin the season, which started with an upset at Penn State.
Beau Blankenship was limited to 22 yards on 12 carries after running for a single-season school record 1,604 yards last year, and Tyler Tettleton threw for just 140 yards on 11-of-23 attempts in the humbling loss.
"We need to move on from this one. Obviously we can't be pleased," Ohio head coach Frank Solich said. "We have to understand that we played a poor football game."
Bridgewater was in midseason form from the start, connecting on all six of his attempts for 77 yards on the game's opening drive and capping it with a 34- yard bomb to Copeland in the end zone while rolling to his left.
Bridgewater hooked up with Copeland again midway through the opening quarter, purposely throwing behind his receiver at the right pylon for a 19-yard TD.
The Cardinals took their time on their next touch, and on the 11th play of the 86-yard march, DeVante Parker was left open for a 27-yard touchdown reception for a 21-0 Louisville lead less than two minutes into the second quarter.
The only blemish for Bridgewater came when he was intercepted by Xavier Hughes on a pass over the middle, but Ohio failed to convert the turnover into points when Matt Green missed a 32-yard chip shot.
Bridgewater made up for his miscue by finding De La Cruz on a corner route that turned into a 40-yard touchdown with 3:44 remaining in the half.
Dyer, the 2011 BCS National Championship Game MVP, made his presence felt in his first game for Louisville with a long TD run early in the second half, and Bridgewater, still throwing midway through the third, capped his big day with a 25-yard scoring strike to Robert Clark.
Ryan Boykin spoiled Louisville's shutout bid on the final play of the third quarter with a 10-yard touchdown run.
Will Gardner relieved Bridgewater to begin the fourth and added a 30-yard touchdown pass to De La Cruz.
Louisville amassed 615 yards and held the ball for 37:16 ... Bridgewater completed 23-of-28 passes ... De La Cruz had a game-high 116 yards on four receptions, while Copeland caught six passes for 98 yards ... Louisville has won seven straight non-conference games ... These teams met for the first time since 1959 ... Louisville hosts Eastern Kentucky next Saturday ... Ohio has its home opener next Saturday against North Texas.