The No. 15 Cougars trailed through the first quarter but Greg Ward Jr. and the offense quickly took over in the second. The elusive Ward Jr. found Duke Catalon on a 15-yard touchdown pass to put Houston ahead 13-10.
Perhaps the turning point of the game came on a failed field goal attempt for the Sooners. Houston's Brandon Wilson returned the missed field goal 100 yards to put the Cougars up 26-17 in the third quarter.
"I really thought I was out of bounds when I caught it. No whistle and a lot of green grass," Wilson said.
Head Coach Tom Herman says the play was all about the "trust factor."
"That was a very captain-like play that he (Wilson) made," Herman said.
From there, the Coogs never looked back.
Ward Jr. finished the game with 321 yards passing with two touchdowns. On the ground game, Catalon carried the Cougars with 88 yards on 22 carries.
Oklahoma's Baker Mayfield threw for 323 yards and two scores.
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Houston will face Lamar next Saturday at TDECU Stadium.