Ward earlier hit Linell Bonner for a 22-yard TD during a wild fourth quarter that began tied 17-all before the teams erupted for 31 combined points. The Cougars ultimately got the final word in the back-and-forth contest thanks to their mobile junior QB and special teams, which partially blocked John Wallace's 53-yard field goal attempt with 54 seconds remaining to seal the signature win for first-year coach Tom Herman.
Houston (2-0) outgained Louisville 462-395 and recorded four turnovers and broke a three-game losing streak to the Cardinals (0-2). Brandon Wilson also returned a kickoff 100 yards for a touchdown.
Ward combined for 334 yards on offense, completing 23 of 33 attempts for 236 yards with one interception. He also carried 21 times for 98 yards.
Kyle Bolin relieved freshman Lamar Jackson in the fourth and twice rallied Louisville with TD drives including his 29-yard scoring pass to Micky Crum with 6:25 remaining. But he couldn't complete a fifth rally as the Cardinals fell to 0-2 for the first time since 1998.
Bolin was 10 of 18 passing for 157 yards and led a touchdown drive ending with Jeremy Smith's 4-yard run for a 24-20 lead early in the fourth.
Jackson was 17 of 27 for 168 yards and a TD in his first start but threw two deep interceptions, one of which led to Kyle Bullard's 21-yard field goal for Houston. The Cardinals also lost two fumbles to the Cougars.
The Cardinals hoped to rebound from last week's 31-24 loss to No. 6 Auburn with a strong effort that would carry them into Thursday's Atlantic Coast Conference showdown against No. 12 Clemson. Louisville was a 13-point favorite but took nothing for granted after self-destructing at the start last week against the Tigers and having to battle back.
Self-inflicted errors doomed the Cardinals again, the worst thing that could happen with a dual-threat quarterback such as Ward.
Ward continually made Louisville defenders miss with nifty moves running the ball and maneuvered into position to find receivers. Houston's quick pace - reflective of Herman's philosophy that helped Ohio State win last year's national championship as offensive coordinator - also kept the Cardinals on their heels for much of the game.
A week after combining for 382 yards and three touchdowns in the Cougars' 52-24 rout of Tennessee Tech, Ward needed just 93 seconds to lead Houston toward a 7-0 lead on its first possession, capping the 51-yard, six-play drive with a 29-yard pass to Steven Dunbar.
Jackson showed a crowd of 50,019 glimpses of his dual skills that helped him beat out favorites Reggie Bonnafon, Will Gardner and Bolin for the start, but freshman mistakes showed throughout.
The freshman ran and threw for many of Louisville's 75 yards on its game-tying first-quarter drive, including his 1-yard TD run. But Louisville's offense stalled, leading coach Bobby Petrino to start Bolin in the fourth quarter.