Blackmon had 173 yards receiving and a touchdown and also scored on a 69-yard run in his return from a suspension, leading the Cowboys to a record-setting offensive day and a 55-28 win against No. 22 Baylor on Saturday.
Brandon Weeden threw for a school-record 435 yards and three scores, Kendall Hunter rammed in a pair of 1-yard touchdown runs and Oklahoma State (8-1, 4-1 Big 12) set a new school mark for total offense for the second time this season by gaining 725 yards.
And that doesn't even include Justin Gilbert's 93-yard kickoff return for a score.
"It was one of those days where everything worked, so obviously there was a good plan, the players bought in and things just worked," coach Mike Gundy said. "Sometimes that happens, and when that happens it's usually a pretty good day."
The Bears (7-3, 4-2) and Cowboys were picked to finish at bottom of the Big 12 South at the start of the season, but there were unexpected title-game ramifications for this November showdown. Instead of meeting to decide last place in the division for a fifth time, the first meeting with both teams in the Top 25 was with first place on the line.
Oklahoma State took a half-game lead over No. 11 Oklahoma (7-1, 3-1), which played later Saturday at Texas A&M. The in-state rivals meet Nov. 26 in Stillwater, but only after the Cowboys travel to Texas and Kansas.
"Obviously, this is a great win. We're in a great position," Weeden said. "But with three left to go in the regular season, we've got to stay hungry."
Robert Griffin III had 267 yards on 30-of-48 passing but Baylor's dual-threat quarterback was largely contained by the Cowboys. Terrance Ganaway and Jay Finley combined for 151 yards rushing with two TDs apiece, but all of the Bears' scoring came after Oklahoma State had built a 34-0 lead.
The Bears were coming off their first win at Texas since 1997 and seeking their first four-game conference winning streak since 1986-87.
"They were smoking hot coming in here," Gundy said. "They played as well as they have in how many years down there? I think coach [Art] Briles has done a great job and their players were believing. They felt really good about themselves, justifiably so."
Three first-half turnovers contributed to the demise of the Bears, who fell a half-game out of first place.
"If my math is right I think there is still a good chance," Briles said. "Our focus right now, honestly, is getting ready to play well next week against Texas A&M at home. That is our focus.
"We have to get this taste out of our mouth."
Blackmon came back from a one-game suspension stemming from his arrest on a DUI charge and surpassed 100 yards receiving for the eighth straight time, tying the school record set by Hart Lee Dykes in 1988.
He also added to the nation's best receiving average, which had been 158.9 yards per game, and tied his career best with 13 receptions. Bo Bowling set a new career high for the second straight week with 101 yards receiving, and Colton Chelf and Josh Cooper added touchdown catches.
"[Blackmon] can really stretch the field vertically, which opens up stuff underneath," Weeden said. "He's dangerous, and I was glad to have him back."
Blackmon was not allowed to speak to reporters.
"We put it behind us, and the only thing he can do now is continue to contribute to this team and this university and do the right thing," Gundy said. "That's what he did this week, and that's why he played."
Weeden was 34 for 42 to break the school record for completions in a game. He threw an 8-yard pass to Chelf to start the Cowboys' final drive and break Zac Robinson's record of 430 yards against Texas in 2007.
Until midway through the third quarter, only one of the Big 12's top two offenses could get anything done.
Blackmon caught a 5-yard TD pass on a fade from Weeden in the back, right corner of the end zone to go with Hunter's two TDs as the Cowboys pulled out to a 24-0 halftime lead. Oklahoma State scored on four of its six first-half possessions -- and the other two ended with Blackmon dropping a would-be touchdown pass on fourth down and Dan Bailey missing his first field goal in 18 tries this season.
Blackmon tacked on another score on the first play of the second half, taking a pitch from Weeden and racing 69 yards down the left sideline for his first career rushing touchdown. He was leading the nation in TD catches this season before adding his 15th against the Bears.
Baylor squandered two scoring chances in the first half with turnovers and couldn't mount a response until Bailey's 23-yard field goal made it 34-0.
Johnny Thomas prevented the Bears from getting on the scoreboard by cutting in front of a seemingly open Krys Buerck in the end zone to intercept Griffin's pass for Baylor's third turnover of the half. Brodrick Brown also stripped Josh Gordon and Shaun Lewis knocked the ball free from Finley.
"We are both good football teams, but we made mistakes and they didn't. The turnovers made a big difference in the outcome of the game," Griffin said. "We've had mistakes in past games but have been able to bounce back. That didn't happen today."