The Cowboys improve to 8-1 overall and 4-1 in Big 12 play, while Baylor drops to 7-3 and 4-2.
OSU's junior quarterback completed 34 of 42 passes for 435 yards and three touchdowns as the Cowboys set the record with 725 total yards of offense, breaking the previous mark of 722 set earlier this season against Tulsa.
"It was one of those days where everything worked," said OSU head coach Mike Gundy. "Obviously there was a good plan and the players bought in and things just worked. Sometimes that happens and when that happens it's usually a pretty good day."
Weeden completed passes to eight different Cowboys, including throwing touchdowns to Justin Blackmon (5 yards), Colton Chelf (62 yards), and Josh Cooper (20 yards).
Blackmon returned from his one-game suspension to tie a career-high with 13 catches for 173 yards and the TD, and he also scored on a 69-yard reverse on the first play of the second half. In eight games, the OSU sophomore has 75 catches for 1,285 yards and 15 touchdowns.
Bo Bowling had his second consecutive 100-yard receiving game with a nine-catch, 101-yard outing against the Bears.
Weeden had 427 passing yards – three shy of Zac Robinson's record of 430 set against Texas in 2008 – after his 20-yard touchdown pass to Cooper early in the fourth quarter.
Baylor then drove the length of the field to score but OSU freshman Justin Gilbert returned the ensuing kickoff 93 yards for a touchdown, and the Bears again took possession. This time they more than four and a half minutes to drive for a touchdown with less than five minutes to play.
With the Cowboys up 55-28 and just four minutes in the game, Weeden almost didn't get the chance to break the school passing record.
"They brought it to my attention ... that I was three or four yards shy, and they asked me, ‘Do you want it?' I said, ‘Let's get it.' So we knew we were going to try a high percentage throw, get it and get out," said Weeden.
"I stood there (on the sideline) forever because we had the return and the defense, so I was almost like, ‘Don't worry about it. (backup quarterback Clint) Chelf needs some reps.'" he added
OSU offensive coordinator Dana Holgorsen was glad to see Weeden get the chance to break the record.
"He was comfortable in the pocket, he was extremely accurate two weeks in a row, and he took care of the football. He played really well," said Holgorsen.
But the Cowboy defense was just as impressive as Weeden, Blackmon and Co. Baylor had the nation's eighth-best offense entering the game and was held scoreless in the first half, as Bill Young's defense created three first-half turnovers.
"It was probably the most complete game that we've played as a team since (Texas) Tech," Gundy said. "The offense was very good and had one of those days where everything worked. Special teams were good.
"The defense was excellent. I thought that as good as the offense was, I thought the defense was even better in the first half. They didn't have any points at halftime, so that's excellent.
"They wanted to stay in the game (in the fourth quarter) and they get a little upset at the head coach for taking guys out, but it's important at that point that everybody needs to play that has worked extremely hard and is loyal to our football program," Gundy added.
The Cowboys travel to Austin, Texas – where an OSU football team hasn't won since 1944 - to face the Texas Longhorns next Saturday.