Frank Booker added 15 points off the bench and Tyler Neal chipped in 13 for the Sooners (19-7, 8-5 Big 12), who held on for the win when a last-chance 3-point try by OSU's Markel Brown missed the mark.
Ryan Spangler contributed 12 points and 13 rebounds.
Brown finished with 26 points and nine rebounds for the Cowboys (16-9, 4-8), who were again playing without sophomore star Marcus Smart, who served the second of a three-game suspension.
Smart was disciplined after an altercation with a Texas Tech fan last week.
Phil Forte put in 16 points and Le'Bryan Nash added 15 with 10 rebounds.