Ryan Spangler scored a layup with 2:18 to play that gave Oklahoma (13-3, 2-1 Big 12) the lead and then added a free throw to complete the pivotal 3-point play.
Spangler scored 16 points and had 15 rebounds for Oklahoma. The Sooners were led by Buddy Hield's 22 points. Isaiah Cousins scored 17.
Iowa State shot 52.3 percent from the field to 40.6 percent for Oklahoma, but the Sooners hit 13-of-30 shots from 3-point range and outscored the Cyclones at the free-throw line 13-6.
DeAndre Kane led Iowa State with 23 points and nine rebounds. Melvin Ejim scored 21, including a 3-pointer that put the Cyclones ahead 77-76 on the play prior to Spangler's decisive score.