The Jayhawks trailed from the opening kick on the way to a 42-6 loss.
Oklahoma State's Justin Gilbert returned the opening kickoff 100 yards giving the Cowboys a 7-0 lead.
"It hurts a little bit," said Kansas head coach Charlie Weis. "We've been a little slow in the offensive area with scoring points this year, so when you're playing the game you want to keep the score within a certain point range. When we started the game off like that, it was a little deflating. It's still just one play, but can you pick a worse way to start a game?"
The Cowboys made it 14-0 with 8:28 left in the second quarter on Desmond Roland's three yard run.
After falling behind early the Kansas defense played well. The Jayhawks held Oklahoma State to 359 yards on offense. They entered the game second in the Big 12 in offense and averaging 180 yards rushing a game.
Kansas held the Cowboys to just 85 yards on the ground. Eventually quarterback Clint Chelf started to find success to the air.
""It seemed like they played pretty well," Oklahoma State head coach Mike Gundy said of the Kansas defense. "I didn't watch the actual technique and the Xs and Os up close because I'm watching the bigger picture, but it seemed like they came in and made some plays."
"After the first couple of series, they loaded the box on us pretty good and put us in an all-pass situation. To be honest with you, we should've have just gone to two wide receivers and maximum protectors and just threw the ball down the field earlier. We didn't, but they did a good job of loading the box up and slowing down the run."
The Jayhawks scored the only points in the third quarter on a Ron Doherty 40-yard field goal.
True freshman Montell Cozart played a lot after the first quarter. The offense finished with 316 yards but couldn't find the end zone. Cozart gave the Cowboys defense a different look.
Kansas picked up 202 yards rushing and much of that came from the option game with Cozart.
"We didn't defend the load option very well," Gunday said. "Kansas committed to running load option and using clock, and we weren't very good with it. Other than that, defensively, we were very good."
The Jayhawks return home next week to face West Virginia. It is the first home game since playing on the road the last two weeks.
"The key is, when you get knocked down you have to keep getting back up no matter how many times you get knocked down," said safety Cassius Sendish. "Until you get knocked out, and I don't ever see us getting knocked out as a team, or a unit, or a defense, or even as a secondary. I don't see it happening, so we just have to keep getting up and keep fighting."