NORMAN, Okla. -- Baker Mayfield and the Oklahoma Sooners pushed aside one last overmatched opponent.
Mayfield completed 23 of 31 passes for 342 yards and three touchdowns and ran for a score to help the Sooners (No. 15 CFP, No. 14 AP) beat Iowa State 52-16.
Samaje Perine ran for 95 yards and a touchdown on 13 rushes, and Joe Mixon rushed for 88 yards and a touchdown on eight carries for Oklahoma (8-1, 5-1 Big 12).
The Sooners have won four straight, outscoring their opponents 232-50. They have surpassed 50 points in four consecutive games for the first time since 2008.
Now, the Sooners can turn their attention to their difficult stretch run in which they face each of the Big 12's top three teams. They are at No. 6 Baylor next week, take on No. 8 TCU on Nov. 21, and finish at No. 14 Oklahoma State Nov. 28.
"We've been in a big atmospheres and big games," offensive coordinator Lincoln Riley said. "The guys have a good trust we don't need to do anything special. The whole team has bought in. ... If we keep winning, the games will get more important."
Joel Lanning completed 26 of 51 passes for 260 yards and a touchdown for Iowa State (3-6, 2-4). The Cyclones have lost four of their last five.
"That's a really good football team we played, and to beat a team like that, you can't make many mistakes," Iowa State coach Paul Rhoads said.
Oklahoma utilized a quick-strike, big-play offense that produced six touchdown drives of five or fewer plays -- three in the opening quarter. After building a 21-3 first-quarter lead, the Sooners led 21-9 at halftime, then pulled away by scoring on all three of their third-quarter possessions.
"We were able to catch our rhythm and got on task moving the ball," Oklahoma coach Bob Stoops said about the third quarter. "We had a few series where we had some big plays."
The Sooners also played stifling defense, holding Iowa State to three first-half field goals and no second-half points until Lanning's 13-yard touchdown pass to D'Vario Montgomery with 5:08 remaining. Top running back Mike Warren, who averaged 154.3 yards rushing and 6.4 yards per carry over the previous six games, was held to just 43 yards on 18 carries -- a 2.4 average.
"It was excellent," Stoops said about his defense. "We don't surrender a touchdown until the last drive with a lot of backups in. What we said all week was that we can't allow them to run the football, and if we could take that away, it could be difficult for them, and it was."
Cyclones receiver Allen Lazard acknowledged that the sub-par running game, which gained 114 yards total on 38 rushes, hindered the offense significantly.
"It's very hard and frustrating," said Lazard, who had eight receptions for 101 yards. "The past few games, we've had 200 yards rushing every game, so struggling to run the ball makes it harder to pass. They just did a good job of packing the box and making the right calls when we would run the ball."
Cole Netten gave Iowa State a 3-0 lead with a 43-yard field goal on the game's opening possession, but Oklahoma answered immediately, with Mayfield connecting with Dimitri Flowers on a 75-yard touchdown pass on its first play from scrimmage.
After Dakota Austin intercepted Lanning's pass near midfield and returned it to the 27, Mayfield needed just one play again to find Dede Westbrook over the middle for a touchdown pass with 5:53 left in the first quarter.
On the Sooners' next possession, it took five plays before Mayfield scrambled out of the backfield on third-and-9 with a 17-yard touchdown run to make it 21-3.
Oklahoma's Austin Seibert punted on the first play of the second quarter, marking the first time in eight quarters and 32 possessions that happened. His previous punt came on the first drive of the Sooners' 63-27 victory over Texas Tech on Oct. 24.
Oklahoma would go on to also punt on two of its next three possessions, with the other one ending when Seibert's 39-yard field goal attempt plonked off the left upright.
Netten's field goals from 45 and a career-long 51 yards pulled the Cyclones to 21-9 going into halftime.
"In the second half, when we lost our rhythm to match theirs, they hit us on the big plays," Rhoads said about Oklahoma's third-quarter spree.