Potts started the game, but after throwing an interception and stalling on multiple plays, head coach Mike Leach pulled him in favor of Steven Sheffield, who was cleared to play after having surgery on his foot three weeks ago.
Sheffield wasn't able to ignite the offense either, throwing two picks in his time on the field.
Potts finished the night with 190 yards on 19-of-35 passing and one touchdown, while Sheffield threw for 117 yards and one score, completing 16 of his 23 attempts.
The Red Raider defense was able to contain the Cowboys during the first half but allowed two time consuming drives, both of which ended in points for the Cowboys in the third and fourth quarters.
Sheffield's pick six with 8:06 left in the game seemed to seal the win for OSU, but Potts returned to the field and was able to lead the Red Raiders downfield for a touchdown on the ensuing drive, pulling them within seven.
Oklahoma State then drove downfield and was poised to score, but a violent collision between the Cowboys' quarterback Zac Robinson and cornerback Jamar Wall resulted in a fumble which the Red Raiders recovered.
With 98 seconds left to go in the game, Potts and the offense tried for one last shot at the end zone but fell short when WR Tramain Swindall dropped a pass on fourth down.
Defensively, the Red Raiders allowed 333 total yards, 243 of them coming on the ground.
On offense, Texas Tech finished the night with 307 passing yards and 50 yards rushing.
The loss drops the Red Raiders to fourth place in the Big 12 South with a conference record of 3-3. They will head home next week to take on the Oklahoma Sooners.