Chris Brown ran for three touchdowns and DeMarco Murray ran for two more as the Sooners (10-1, 6-1 Big 12), who lost to fourth-ranked Texas earlier in the season, moved into a three-way tie with Texas Tech and Texas atop the Big 12 South Standings.
Oklahoma went into the game fifth in the BCS, behind Alabama, Texas Tech, Texas and Florida.
Texas Tech (10-1, 6-1) went into Saturday's game ranked third in scoring offense in the nation at 47.9 points per game. But Oklahoma's defense bottled up Graham Harrell early while the Sooners were building a 42-7 halftime lead.
Harrell threw for three touchdowns, but the Red Raiders, who were riding the nation's longest winning streak at 12 games, were no match for the Sooners.
Texas Tech is at home vs. Baylor next Saturday. Assuming the Red Raiders win that game, they would have to wait for the outcome of the Oklahoma-Oklahoma State game that night to determine their title prospects.
An Oklahoma State win would give the Red Raiders the South title. Missouri has already won the Big 12 North division.
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