And extend OU's winning streak to 28 games when coming off a regular season loss.
"Well, we've been fortunate...it's just the process of winning, it's not like you change it," said OU head coach Bob Stoops.
Something else Stoops did is tie legendary Sooners head coach Bud Wilkinson atop the all-time wins list at 145 career victories.
"I've got the greatest respect for what Coach Wilkinson did, from the stories I've heard from his players," Stoops said. "Coach Wilkinson really started all the national championships and conference championships and he's still [a legend]. So, I'm not one to quantify. I'm still working."
In order to do so, the Sooners had to respond to a poor start that featured a failed fourth down attempt inside the five and a couple ISU penalty-aided first downs on personal fouls.
Quarterback Landry Jones took care of that, driving his offense 90 yards on 12 plays and capping it off with a 20-yard touchdown strike in the corner of the end zone to wide receiver Sterling Shepard midway through the second quarter.
On the ensuing drive, though, Jones had his troops moving until he errantly threw into the hands of ISU defensive back Durrell Givens on a double move up the sideline intended for wide receiver Kenny Stills.
That set up the Cyclones for a 27-yard field goal by place kicker Edwin Arceo.
Jones' second mistake of the game on a tipped pass and pick set up Arceo for his career long of 51 yards and a 7-6 game.
But the Sooners quickly responded before the half.
Moving 75 yards in four plays, Jones hit Stills for a 21-yard strike in the front left corner of the end zone, making it 14-6 at halftime.
OU came out with a strong drive in the second half, converting a fourth down and 3-of-4 third downs, the latest of which was a 20-yard touchdown pass to Justin Brown, who showed incredible concentration by snatching it after it hit off an ISU defender.
Back came the Cyclones, however, when Jantz directed his offense down the field and a wide receiver reverse to Jarvis West went 19 yards for a score and 21-13 deficit.
The Sooners quickly expanded the advantage again to double digits on a drive powered by running back Brennan Clay.
As part of his monster day, he carried five times for 41 yards and finished it off with a bruising 18-yard touchdown run to push the mark to 28-13.
"It's kind of one of those deals, it's the next guy up," Jones said. "We leaned on Brennan today and he stepped up for us."
It was 35-13 when Jones connected with Stills for the pair's second touchdown hookup of the contest early in the fourth, this time a 31-yard toss.
The Cyclones scored one more time when running back Shontrelle Johnson completed a 9-play, 83-yard drive on a 2-yard touchdown rush.
Jones, who recorded his 10th career 400-yard day, finished 32-of-45 for 405 yards and four two touchdowns along with the two interceptions.
Clay had a career day, breaking the 100-yard plateau for his first time as a Sooner while scampering for 157 yards and a touchdown on 24 carries.
"I'm just thankful," Clay said. "I'm blessed and I thank the Lord every day for that...I came out this game, prepared all week. I was fortunate."
Brown led the OU receiving game with seven catches for 107 yards and a touchdown.
For ISU, Jantz finished 20-for-40 for 191 yards with a pick.
Johnson led the Cyclones in rushing with his seven rushes and 28 yards, while wide receiver Quenton Bundrae paced the receiving attack with four catches for 44 yards.The Sooners (6-2, 4-1 Big 12) now return home to face Baylor at a time to be determined, while ISU (5-4, 2-4 Big 12) heads to Austin to take on the Texas Longhorns at 11 a.m.