The Cowboys saw their hopes for a share of the Big 12 Conference title disappear after trimming a 10-point halftime deficit to two with 4:30 to play.
Clyburn scored 20 points, hitting 7-of-10 from the field while grabbing five rebounds and handing out five assists.
The Cyclones (20-10, 10-7 Big 12) hit 50 percent of their shots overall. Georges Niang added 18 points for Iowa State.
Marcus Smart had 24 points to lead the Cowboys (22-7, 12-5). Kansas and Kansas State share the conference lead at 14-3.
After Oklahoma State closed within 70-68, Iowa State went on an 11-2 run to put the game away.