Markel Brown led the way with 20 points for eighth-seeded Oklahoma State (21-11), which advances to play No. 1 seed Kansas in Thursday's quarterfinal round. Phil Forte and Le'Bryan Nash added 14 and 10 points, respectively.
For ninth-seeded Texas Tech (14-18), Jaye Crockett poured in 20 points, while Dejan Kravic tallied a double-double with 18 points and 12 rebounds.
Oklahoma State set the tone early, shooting 52.2 percent from the field in the first half while knocking down 17 free throws, as it carried a 46-23 lead into intermission.
The Cowboys regressed to 45.5 percent from the floor in the second stanza, but their advantage never dipped below 16.
Texas Tech was plagued by a game-high 17 turnovers, which Oklahoma State converted into 24 points.