The Cowboys were attempting to win their first outright conference title since the 1948 team won the Missouri Valley Conference crown.
OSU, 10-2, will now wait until next week to find out where and whom it will play in a postseason bowl game.
"It was a tough loss. I hated that we didn't play well in the last three minutes. We gave up big plays," said Oklahoma State head coach Mike Gundy.
The Cowboys certainly had their chances midway through the fourth quarter despite giving up a 17-play drive and a 15-play drive that led to OU field goals, giving the Sooners a 30-24 lead. But Brandon Weeden's pass on the Cowboys first play from scrimmage was deflected by Ronnell Lewis and intercepted by Austin Box, and four plays later a 26-yard field goal by Jimmy Stevens gave the Sooners a nine-point advantage.
Gundy's team would never get the ball back with a chance to go ahead.
Weeden threw a 15-yard touchdown pass to Justin Blackmon, who finished with eight catches for 105 yards despite being hampered by an ankle injury all night, to pull the Cowboys within 33-31 with 4:06 remaining to play.
OU took over on its own 16-yard line after a holding penalty on the kickoff return. The game's deciding play occurred two plays later when Cowboy cornerback Brodrick Brown dropped a interception on Landry Jones' deep throw. On the very next play, Jones found Cameron Kenney cutting across the middle of the field on a third-and-12 play and the Sooner receiver outran everyone 86 yards for what many assumed was the game-deciding TD.
But the game was far form over as OSU freshman Justin Gilbert caught the ensuing kickoff on his 11-yard line and raced 89 yards to pull the Cowboys within 40-38 with 2:51 still showing on the clock.
Jones made another big throw – and this time it was the nail in the Cowboys' coffin – when he found tight end James Hanna wide open behind the OSU secondary for a 73-yard catch and run for a touchdown to put the Sooners up 47-38.
Weeden and the Cowboys drove to the OU 17 where Dan Bailey converted a 34-yard field goal with 36 seconds remaining. But Sooner receiver Ryan Broyles recovered the onside kick and OU ran out the clock, and spoiled OSU's hopes of winning the Big 12 title.
"I wouldn't say we blew an opportunity. We played a football game. I told the team that," Gundy said.
"The reason we had that opportunity is because they won 10 games prior to this, so they put themselves in a situation where they had a chance to play for the conference championship game. We certainly would have liked to have taken advantage of the opportunity we had to play next week, but the way these guys have played this year, grew and came together, I wouldn't say they have blown an opportunity. We just didn't take advantage of one."
Weeden completed 28 of 43 passes for 257 yards and two touchdowns but also threw three interceptions. He now has 32 passing touchdowns this season, which breaks the previous record of 31 set by Josh Fields in 2002.
Blackmon tied an NCAA record by recording his 11th consecutive game of 100 receiving yards with at least one touchdown. He now shares the record with Aaron Turner of Pacific, who achieved the feat in 1991.
"Justin didn't practice all week. Justin didn't take one snap. I will suspect he'll be pretty sore tomorrow," said Gundy. "He has a very high tolerance of pain. He wanted to play. If there had been any chance of injuring him further, we wouldn't have played him. It wasn't that type of injury and he wanted to play with the pain, so we really couldn't keep him out of there. That's not an excuse. That's not the reason we lost the game."
The Cowboy defense forced three Sooner turnovers – two interceptions by freshman linebacker Shaun Lewis and one by Brodrick Brown – but allowed 588 total yards on 107 plays, including an astounding 60 in the first half.
The Sooners were good on 16 of 27 third-down conversions.
"That was a big part of the game. I knew they were successful on third down but I didn't realize we gave up 16 third-down conversions. That's way too many," said Gundy. "We've got to be much better. We have to get pressure on the quarterback. In that area, it looked like the first four games of the year when we didn't do a good job on third down."
Gundy said that he is still proud of his team despite Saturday night's loss.
"I was proud of the team, (and) the way we fought back. To go down by two scores and then return the kick and put ourselves right back in the game. We need to play better in crucial situations. At the very end they made plays and we didn't. Really that's what it comes down to," said Gundy.
"I told the team that as difficult as it is, this needs to be a learning experience for them. In those situations we need to make sure we're in the right spot, in the right coverage, covering everything up, and try to learn from our mistakes.
"Again, I was very proud of our team and the way they competed. I just hate we came up a little bit short."