NORMAN, Okla. -- Baker Mayfield threw up his hands in celebration before the ball even landed in his receivers arms.

When Mayfield arrived on the sidelines after his 75-yard touchdown pass on Oklahoma's first offensive play of the game, he was greeted by injured cornerback Zack Sanchez with the reward of a piece of bubble gum.

Sanchez was passing out plenty of treats Saturday as the No. 15 Sooners blew out Iowa State 52-16 in front of 85,595 at Gaylord Family-Oklahoma Memorial Stadium on Saturday.

"I had no idea he (OU offensive coordinator Lincoln Riley) was going to call that the first play, but hats off to him," Mayfield said. "When you do that, you don't always expect it to work out perfectly the way it did in practice."

Mayfield threw for 342 yards and three touchdowns, Durron Neal had a career-high 10 catches and running backs Samaje Perine and Joe Mixon combined for 183 yards on the ground as Oklahoma won in a blowout for the fourth consecutive game.

The tone looked set on that first offensive play when Perine took the handoff and flipped it to receiver Sterling Shepard, who gave it back to Mayfield.

Mayfield then lofted a long pass to a wide open Dimitri Flowers for a touchdown.

It wound up being one of five Sooners touchdowns scored on drives that lasted less than a minute. Only one of those drives were less than 55 yards and three came on the first play of the drive.

"They were an aggressive defense," Sooners offensive coordinator Lincoln Riley said. "That's what you've got to do against aggressive teams."

Since losing to Texas on Oct. 10, the Sooners have outscored their last four opponents 232-50.

But that streak has been against the teams at the bottom of the Big 12 standings.

That stretch is over.

The Sooners take on No. 6 Baylor next week before facing TCU and Oklahoma State to close out the regular season.

"It's just another one," Riley said. "It really is to us. This one was darn important tonight. I know people don?t want to hear that."

For Iowa State (3-6, 2-4) it was a return to struggles a week after shutting out Texas.

The Cyclones couldn't find much running room against the Oklahoma defense, rushing for just 114 yards.

Mike Warren, the Big 12's second-leading rusher, had just 43 yards on the ground.

"That was big," Oklahoma coach Bob Stoops said. "We said all week that was a major key for us, that we can't allow them to run the football, not successfully and consistently."

That was just a start of the offensive deluge for the Sooners early.

By the end of the first quarter, Oklahoma led 21-3 thanks to three quick touchdowns.

Mayfield hit Dede Westbrook for a 27-yard touchdown pass on the first play of the Sooners' third drive, after Dakota Austin's interception.

"That's deflating," Iowa State coach Paul Rhoads said of the Sooners' big plays. "That's a good way to put it."

The Sooners next drive wasn't quite as quick but it was just as effective, going 40 yards in five plays, ending on Mayfield's 17-yard touchdown scramble off a broken play on third and 9.

Oklahoma's defense was just as impressive early, stopping quarterback Joel Lanning and the rest of the Iowa State offense after some early jitters.

The Cyclones twice converted on third down on the opening drive before settling for a field goal. But after that, Iowa State went five consecutive drives without picking up a first down.

NOTES: Cyclones RB Mike Warren finished three yards short of 1,000 for the season. ... Oklahoma LBs Devante Bond and Jordan Evans returned to the starting lineup after absences of four and two games, respectively. ... Iowa State's Reggan Northrup recovered a Samaje Perine fumble early in the second quarter. ... After not registering a sack in the first eight games of the season, Oklahoma DE Charles Tapper has five in the last two games. ... Sooners LG Jonathan Alvarez missed the game with a sprained knee while CB Zack Sanchez missed his second consecutive game with a sprained ankle. Bob Stoops said both were expected to return next week. ... Iowa State hosts Oklahoma State next week.