The Aggies built a 20-3 halftime lead before the Cowboys (4-0, 1-0 Big 12) took advantage of three Texas A&M turnovers and numerous penalties to reel off 27 straight points to take a 30-20 lead.
Jeff Fuller caught a 4-yard touchdown pass with 2:20 remaining for A&M's first score since the second quarter to get A&M within 30-27.
A&M's defense forced a punt and the Aggies (2-1, 0-1) got the ball back with almost two minutes remaining, but Ryan Tannehill threw his third interception to seal the Cowboys' win.
Blackmon ran 39 yards into A&M's end zone for a safety as time expired to leave it at 30-29.
The matchup was oddly similar to last year's matchup between these teams when A&M led 21-7 at halftime before errors led to a 38-35 Oklahoma State win in Stillwater.
''We gave the game away,'' Aggies safety Hunter said. ''We didn't step up and play with the same passion we did in the first half. We weren't going out with that same fire and we weren't ready to fight. Regardless of what they did in the second half ... we just didn't go out and want to win.''
Oklahoma State won its fourth straight in the series and its seventh overall on the road in the first top 10 matchup at Kyle Field since 1975. It marks the first time the Cowboys have won consecutive games in College Station.
It could be the last time these teams meet in conference play with the Aggies likely headed to the Southeastern Conference next season. It was a fact not lost on the few Oklahoma State fans in attendance who chanted, ''Big 12, Big 12'' as the final seconds of the game ticked away.
''It's almost exactly the same scenario, but we had a bigger lead this year,'' Texas A&M coach Mike Sherman said of the second-half collapse. ''They did a great job in the second half - a lot better job than they did. We certainly helped in that regard, but they did a good job.''
Texas A&M kept Oklahoma State's high-powered offense in check through the first two quarters, but looked frazzled and tired dealing with its frenetic pace after halftime.
Several Texas A&M players had cramps and some had to receive IVs at halftime.
''Some guys on defense cramped up, about three or four guys, but that's football,'' defensive end Tony Jerod-Eddie said. ''That's not an excuse for the way we played in the second half.''
Jeremy Smith ran untouched into the end zone on a 13-yard run that cut the lead to 20-10 early in the third quarter. Blackmon's TD catch got the Cowboys within three and they took a 24-20 lead when Weeden found Tracy Moore on a 4-yard pass after an A&M fumble.
Quinn Sharp added two short field goals in the fourth quarter to extend the lead.
Tannehill threw for 309 yards and two scores and ran for another touchdown and Ryan Swope had 105 yards receiving for A&M.
''We had so much on the line coming into this game and we were so excited,'' Tannehill said. ''Any loss is tough, but this one especially hurts.''
On Blackmon's score in the third quarter, Weeden found him in the corner of the end zone, but he dropped the ball well out of bounds and officials first said it was an incomplete pass. Blackmon yelled at an official that it was a touchdown as he walked away and after a review, the star receiver ended up being right. It was an 11-yard touchdown pass and Oklahoma was within 20-17.
The Cowboys were helped earlier in that drive when A&M's Jonathan Stewart hit Anyiam when he was out of bounds and the penalty tacked on 13 yards to the 9-yard reception.
Kenric McNeal caught a 33-yard pass from Tannehill on the second play of A&M's next drive, but fumbled, giving the Cowboys the ball right back.
They took advantage of the error and got their first lead of the game, 24-20, when Weeden hit Moore in the back of the end zone for the TD.
On a repeat of their last drive, Texas A&M just got one play in before turning the ball over on the second. This time Tannehill was intercepted by Brodrick Brown.
The Aggies caught a break, though when Blackmon caught an 8-yard pass and was heading toward the end zone when he fumbled at the 2-yard line and the ball rolled out of the back of the end zone for a touchback.
But Texas A&M didn't get anything out of it when Tannehill threw another interception on the next drive which Oklahoma State converted into a short field goal that pushed the lead to 27-20 early in the fourth quarter.
Tannehill got A&M going on the fourth play of the game when he faked a handoff to Cyrus Gray and dashed 65 yards up the middle for a touchdown to make it 7-0.
The Aggies put together a 10-play, 86-yard drive capped by a 17-yard touchdown pass to Fuller to go up 17-3 early in the second quarter.