Friendly adversaries throughout their sterling college careers, their rivalry will be rekindled Thursday night (8:20 p.m. ET, Fox) in a key AFC North showdown pitting Rudolph's Pittsburgh Steelers against Mayfield's Cleveland Browns.
"It's interesting, especially because now it's division rivals as well, not just from college," Mayfield said. "I'm looking forward to it."
According to Elias Sports Bureau research, never before have quarterbacks from the Oklahoma Sooners and Oklahoma State Cowboys started against each other in the NFL. Fittingly, it will be the two most prolific passers from each side of the Bedlam Series making that history.
"Great player, competitor," Rudolph said of Mayfield. "Fierce competitor."
That competition dates to 2015, when Mayfield won the starting job at Oklahoma as a walk-on transfer from Texas Tech. The year before, injuries propelled Rudolph to the starting role at Oklahoma State as a true freshman late in the season.
With Mayfield and Rudolph leading the way, Bedlam became the biggest regular-season game in the Big 12 and one of the biggest in all of college football during their three years facing off against each other.
In all three, Mayfield's Sooners got the best of Rudolph's Cowboys.
"Your rival games hurt more when you lose, for sure," Rudolph said. "You wouldn't be human if you said otherwise."
Thursday night at Cleveland's FirstEnergy Stadium, Rudolph looks to return the favor. Thanks in part to his emergence, the Steelers have rallied since losing star quarterback Ben Roethlisberger to a season-ending injury to his throwing elbow to crawl back into the playoff picture. Pittsburgh beat the Los Angeles Rams on Sunday for its fourth straight win. Rudolph, a third-round pick in 2018, delivered perhaps the best performance of his NFL career in that victory, passing for 242 yards and a touchdown without an interception.
"Playing against Mason, you know exactly what type of player he is," Mayfield said. "He's a leader, his teammates love him -- he's having success for those reasons."
Mayfield is coming off his defining moment of this season as well, leading the Browns on a late winning touchdown drive to defeat the Buffalo Bills on Sunday.
The winner of Thursday's game will take a big step forward in keeping their playoff hopes alive. And the game will be closely followed in Oklahoma, where Mayfield and Rudolph remain immensely popular.
"There's some excitement here," said Oklahoma State coach Mike Gundy, who coached Rudolph and called Mayfield the best Oklahoma quarterback he ever coached against. "A pretty cool deal for both schools."
Especially considering the history.
Before they ever faced off on the field, the two became friendly off of it through mutual buddies.
Oklahoma quarterback Trevor Knight, whom Mayfield later beat out, and Oklahoma State wide receiver Austin Hays, who became one of Rudolph's favorite receivers, were best friends from high school in San Antonio.
Through Knight and Hays, Mayfield and Rudolph saw each other occasionally on offseason weekends, sometimes in Norman, sometimes in Stillwater.
"Trevor and I have been best buds forever, and because of that we started hanging out with a lot of the Oklahoma guys and vice versa," Hays said.
That led to a group text chain, which included several players from both teams, and eventually evolved into spring break plans in 2015 to Destin, Florida.
"We all stayed together in this big three-story house and became pretty close," Hays said.
Mayfield noted that the highlight of that vacation proved to be Bedlam beach wrestling in the sand, with Oklahoma State tackle Zachary Crabtree taking on Oklahoma lineman Christian Daimler. Crabtree won that bout, which was recorded on a cellphone. Later on, Gundy even played it in the team room for his players.
"Spring break is always a fun trip, great time in college," Rudolph said. "You make a lot of memories that you'll hold the rest of your life."
Rudolph and Mayfield made plenty of memories throwing the football as well.
In 2015, they both had breakout campaigns, catapulting their teams into Big 12 title and College Football Playoff contention. On Thanksgiving weekend, the two met in Stillwater with the Big 12 championship on the line. But going in, Rudolph suffered a broken foot, which prevented him from starting. He wound up attempting only three passes, one of which was intercepted and returned for a touchdown.
Mayfield, meanwhile, grew the first of his many mustaches for Bedlam, a signal to the Cowboys that, in his words, "a new sheriff was in town." With Rudolph ailing, Mayfield and Oklahoma rolled to a 58-23 win, which propelled the Sooners to the playoff.
The following year, Rudolph finished with more than 4,000 yards and only four interceptions. Mayfield became a Heisman finalist. And once again, the meeting of their teams decided the Big 12. Rudolph was healthy this time, but Oklahoma State struggled to get its air attack going in the rain, and Mayfield prevailed again, this time 38-20. During the game, Mayfield actually wore an undershirt with the words "Back to Back 2015 & 2016" under his pads, as if the result was already a foregone conclusion.
"He was like a conductor," Pittsburgh wide receiver James Washington, who starred alongside Rudolph at Oklahoma State, said of Mayfield. "The guys that he was around, he just added to how good they were."
In 2017, Rudolph and Mayfield were better than ever, topping the country in QBR leading into Bedlam.
This time against the Sooners, Rudolph played one of the finest games of his college career, passing for 448 yards and five touchdowns. Mayfield, however, outdueled him again, with 598 yards and six total touchdowns in a thrilling 62-52 barn burner. Oklahoma went on to a third consecutive Big 12 title on the way back to the playoff, and Mayfield won the Heisman Trophy.
"The last one I played with him in college was a good one, an exciting one, but I think it's all a little bit different now," Mayfield said. "I'm sure as the years go on, we will continue something, but it's different now."
This week, Rudolph tried to downplay those Bedlam losses serving as extra motivation for their first NFL meeting.
Knowing Rudolph, Mayfield wasn't exactly buying it.
"I think he's a guy that has a big chip on his shoulder, which is why we got along," Mayfield said. "He's more reserved than I am.
"But I'm sure he's looking for revenge."
ESPN Steelers reporter Brooke Pryor contributed to this report.