The Cyclones (6-4, 3-4 Big 12) overcame a 17-point deficit to beat the Cowboys (10-1, 7-1 Big 12), opening a path for the Oregon or Alabama to face LSU in a rematch for the title.
''This one stings. This one's tough,'' said Oklahoma State quarterback Brandon Weeden, who threw three interceptions.
None of those stung more than his first pass in the second overtime, which was intercepted by Ter'Ran Benton. Woody ran for 6 and 15 yards, then bullied his way into the end zone to give the Cyclones their first victory over a top-five opponent in school history.
Weeden threw for 476 yards, but the Cowboys' offense turned it over five times.
''I hate it for the guys. But it's real simple. If you lose the turnover battle in such a big fashion, it's extremely hard to win a game, especially on the road,'' Oklahoma State coach Mike Gundy said.
Playing a day after Oklahoma State women's basketball coach Kurt Budke and three others were killed in a plane crash, the Cowboys were 27-point favorites against the upstart Cyclones.
Iowa State lost its first four Big 12 games and entered play 0-56-2 against teams ranked sixth or higher in The Associated Press poll.
Cyclones coach Paul Rhoads has had some signature wins in his three seasons in Ames — but none as big as this.
''We got a group of young men that put their hard hats on every day and just continue to go to work,'' Rhoads said. ''I could not be prouder of the effort they put out tonight.''
Iowa State freshman quarterback Jared Barnett found James White for a 25-yard touchdown on the first play of extra time, but Weeden answered with a 6-yard TD pass to Josh Cooper.
Benton's interception set up a thrilling finish for the Cyclones and Rhoads, the defensive coordinator at Pittsburgh when it upset No. 2 West Virginia in 2007.
Barnett finished with 376 yards passing and three TDs for Iowa State..
Oklahoma State stretched its lead to 24-7 less than 3 minutes into the second half and looked set to break it open as it usually does. Tracy Moore caught Weeden's pass in traffic and stumbled 30 yards for the touchdown.
That could have been it for Iowa State — but the Cyclones were far from finished.
Iowa State answered with a 32-yard TD run from White and Zach Guyer's 24-yard field goal made it 24-17 with 4:04 left in the third quarter.
Oklahoma State came in averaging 51.7 points a game, but it couldn't string together the drives that made Weeden a serious Heisman Trophy contender.
Iowa State took advantage, tying the game at 24 with 5:30 left in regulation when Barnett found a Albert Gary sliding in the end zone for a 7-yard TD catch. Oklahoma State's Alex Elkins intercepted Barnett's pass with 3:17 left, but Quinn Sharp pushed a 37-yard field goal right, just over the upright, with 1:17 to go to force overtime.
It was just the third missed field goal in 20 tries for Sharp.
Iowa State knew it would need a lot of breaks to pull off the upset.
The Cyclones caught a few early, recovering a fumble and intercepting Weeden's pass in the first quarter. But they didn't turn either into points, and the Cowboys' defense made them pay for it.
Linebacker Shaun Lewis jumped Barnett's pass and took it back 70 yards for a touchdown, giving Oklahoma State a 7-0 lead late in the first quarter.
Iowa State pulled to 10-7 on Barnett's 16-yard TD pass to Darius Reynolds. But Blackmon stopped short and went high for Weeden's pass over a pair of defenders on a 27-yard touchdown reception, giving Oklahoma State a 17-7 lead with 5:26 left before halftime.
''They came out ready to play. They came high with the crowd, getting them going. It was a good environment to play in. But this is why we play football, to win in positions like this. We just needed to finish,'' Blackmon said.
Iowa State held a moment of silence before the game to honor Budke, assistant Miranda Serna and two others who were killed Thursday when their single-engine plane crashed during a recruiting trip in Arkansas.
''The plane crash, for the families and people involved, is just tragic, and honestly, I would have said this no matter the outcome of the game. It's so much more important than this game,'' Gundy said. ''These guys wanted to go out and play the best they could for themselves, for us, the fans, and for OSU, and it just didn't come out in their favor tonight.''