Landry Jones threw for 405 yards and four touchdowns as No. 14 Oklahoma downed Iowa State, 35-20, at Jack Trice Stadium on Saturday.
Jones completed 32-of-45 passes with two interceptions for the Sooners (6-2, 4-1 Big 12), who have won 14 straight games against Iowa State.
Justin Brown caught seven balls for 107 yards and a touchdown, while Brennan Clay added a career-high 157 yards and a score on 24 carries.
"It was a well played, good football game. I knew it would be a battle and it would be tough," Oklahoma coach Bob Stoops said. "If you watch (Iowa State), everyone they've played, especially here at home, they've been tight games, so I'm proud of our team to finish the way they did here away from home in a good atmosphere."
The win was the 145th career victory for Stoops, tying him with Bud Wilkinson for second on the Sooners' all-time victory list.
Steele Jantz went 20-for-40 through the air for 191 yards and an interception for the Cyclones (5-4, 2-4), who have dropped four of their last six.
"I think he played well. He gave us an opportunity to be in it and made some accurate throws," Iowa State coach Paul Rhoads said about Jantz. "It wasn't his best decision-making game, but he continues to learn, and we'll continue to coach him."
After forcing Iowa State to punt on the opening possession of the game, Oklahoma marched all the way down to the Cyclones' 5-yard line as Jones found four separate receivers for double-digit gains.
But Oklahoma opted to go for it on 4th-and-1 and Jones was stuffed for no gain on a rush up the middle to turn the ball over on downs.
The teams traded punts from there until the Sooners regained the ball at their own 10 early in the second quarter and Durron Neal's 18-yard catch on a 3rd- and-8 kept the drive alive before Jones capped the 12-play march with a 20- yard touchdown strike to Sterling Shepard in the right side of the end zone with 10:00 left in the half.
Iowa State later took advantage of a turnover to get on the board as Durrell Givens intercepted Jones on Oklahoma's next touch and returned it 47 yards to the Sooners' 15.
The Cyclones would manage just six yards, though, and were forced to settle for a 27-yard field goal by Edwin Arceo.
Givens then picked off a tipped Jones pass on the second play of Oklahoma's ensuing possession to give the ball to Iowa State at midfield, resulting in Arceo's 51-yard kick to bring the Cyclones within 7-6 with 1:04 left in the second quarter.
However, Brown hauled in a 40-yard bomb down the right sideline three plays later to set up Kenny Stills' 21-yard score on leaping grab over a defender on the left side of the end zone on the next play to put the Sooners on top, 14-6, at the break.
"We knew it was going to be a two-minute situation and we would have to take some shots down field. Landry threw it up and that is when he trusts us, so we have to come down with those catches," Brown said.
Oklahoma received the ball to start the third quarter and after converting a 4th-and-1 at its own 45 with a 1-yard rush by Blake Bell, Brown capped the 14- play, 75-yard drive with a 20-yard touchdown grab in the back corner of the end zone.
Iowa State quickly answered with a 6-play, 65-yard trek that was kept alive by a 13-yard scramble by Jantz on a 3rd-and-9 and finished off with Jarvis West's 19-yard touchdown run on an end around to make it a 21-13 game with 5:49 remaining in the third quarter.
But the Sooners responded with another scoring drive to regain their two- possession advantage as Clay's 18-yard touchdown run ended an 8-play, 68-yard march that included just one third down.
Oklahoma put the game away less than five minutes into the fourth quarter when Jones found Stills on the left side of the end zone for a 31-yard score.
Shontrelle Johnson then finished off a 15-play, 75-yard march with a 2-yard push across the goal line to bring the Cyclones within 35-20 with 6:32 left in the game, but they would get no closer as Tony Jefferson intercepted Jantz on Iowa State's next touch.
Oklahoma was able to run out the remaining 3:29 of game clock.
Barry Switzer is Oklahoma's all-time leader in wins with 157 ... The Sooners lead the all-time series between the teams, 70-5-2 ... Oklahoma improved to 41-10 in the month of November under Stoops ... Oklahoma outgained Iowa State, 593-290 ... Stills finished with 92 yards on six receptions ... Quenton Bundrage paced Iowa State's receivers with 44 yards on four catches.