Instead, the Cougars' high-powered offense gained only 41 yards in the second half and Louisville scored on its first two possessions after the break to set up Saturday's 20-13 defeat.
"We didn't get into a rhythm at all in the second half," Houston coach Tony Levine said. "I thought our first-down execution was poor (and) got us into second-and-long calls.
"At the end of the day, we certainly didn't make enough plays to get enough points on the board in the second half to win the game."
The Cougars (7-3, 4-2 American Athletic Conference) had 195 total yards, with 130 coming in their 13-point second quarter. Houston's 121 passing yards are the fewest since it totaled just 119 against SMU on Nov. 19, 2005.
Losing star wide receiver Deontay Greenberry in the first quarter to a head injury was also a factor in Houston's poor outing.
Houston entered the game averaging 38 points a game, but it wasn't just a lack of execution that slowed Houston's attack. Louisville entered the game leading the nation in scoring defense and lived up to billing in shutting out the Cougars in the second half.
"They're a talented defense," Levine said. "They get tackles for loss; they get sacks. They're giving up 10 points a game, so I certainly give them credit as well."
Houston's defense forced just one turnover, a fumble recovery on a muffed punt return, snapping its nation-leading 17-game streak of games with multiple turnovers.
The loss comes after last week's 19-14 defeat at Central Florida, when the Cougars had two passes fall incomplete in the end zone that would have given them a go-ahead touchdown in the final minute.
Houston's latest defeat stemmed from its failure to stop Louisville running back Dominique Brown.
Brown ran for a career-high 137 yards and two touchdowns, including the go-ahead score in the third quarter.
Louisville's Teddy Bridgewater completed 19-of-29 passes for 209 yards but had his streak of 21 games with a touchdown pass end at 21.
John Wallace kicked field goals of 37 and 39 yards for the Cardinals (9-1, 5-1), who outgained the Cougars 332-195.
Against Houston, Brown started both halves with game-changing plays.
After capping Louisville's first drive with a 13-yard touchdown run, the junior provided a 17-13 lead with his second TD run on the opening possession of the second half, just the spark that the Cardinals needed following a lethargic second quarter. Louisville held the ball for 12:24 in the period, and Houston never recovered.
"I felt like we had opportunities, we had possessions offensively to get that done, and we just didn't," Levine said.
Brown's second TD led to frustration for Houston safety Adrian McDonald, who was ejected for punching Louisville offensive lineman Kamran Joyer several times on the play. Houston looked poised to jump on the Cardinals right away when Demarcus Ayers returned the opening kickoff 61 yards with the help of five missed tackles, and the Cougars moved 11 yards for a first down at the Louisville 28. After three straight incompletions, they gambled on fourth down instead of kicking a field goal into the wind.
John O'Korn's slant pass to Xavier Maxwell came up 5 yards short, giving Louisville the ball on downs.
Brown's running quickly got the Cardinals on the board, carrying seven times for 44 yards, including the touchdown run off left tackle. Wallace's first field goal two drives later put Louisville up 10-0.
Houston needed just two drives to tie the game, driving 48 yards for Kyle Bullard's 46-yard field goal and 60 yards ending in Kenneth Farrow's 4-yard run with 6:35 left before halftime. Those drives were telling as the Cougars' no-huddle offense seemed to confuse the Cardinals' defense, which struggled to keep up.
Defensively, Houston succeeded in pressuring Bridgewater, sacking him twice and keeping him on the run at other times.
Two key plays helped the Cougars take a 13-10 lead. The first was Michaelee Harris' muffed punt recovered at the Louisville 39 by Trevon Stewart, who entered leading the nation with eight turnovers.
Cardinals defensive end Lorenzo Mauldin was later penalized for roughing O'Korn, wiping out the turnover and setting up first down at the 24.
Bullard's 22-yard field goal with 25 seconds left in the half provided Houston's only lead.
Back-to-back losses all but eliminate Houston from the AAC title race.
"On the road, sell-out crowd, hostile environment, true freshman at quarterback and lose one of the best receivers in the nation in the first quarter - going forward, I think it's going to help us," Levine said.