OSU (5-1, 2-1 Big 12) scored 17 first-half points after Clint Chelf replaced J.W. Walsh at quarterback, then held on for the victory after TCU cut the lead to seven points in the fourth quarter.
Chelf connected on 10-of-25 passes for 178 yards after Walsh had completed 9-of-18 attempts for 115 yards with two interceptions on three early drives.
Rennie Childs and Desmond Roland each scored a rushing touchdown as Oklahoma State won an eighth straight home game.
Trevone Boykin was limited to 188 passing yards on 17-of-35 efficiency and was picked off three times for the Horned Frogs (3-3, 1-2).