Blake Bell threw for 232 yards and two touchdowns, while the Sooners' stout defense picked off Notre Dame's Tommy Rees three times, as No. 14 Oklahoma downed the 22nd-ranked Fighting Irish, 35-21, on Saturday at Notre Dame Stadium.
The Sooners (4-0) smothered Rees from the start, intercepting back-to-back passes from the Notre Dame signal-caller to help create a 14-0 cushion less than three minutes into the game.
OU linebacker Corey Nelson returned the first pick 24 yards for a score before Frank Shannon intercepted Rees' next throw, setting up an 11-yard touchdown run from Damien Williams, who finished with 42 rushing yards on nine carries.
Bell, making his first career road start, helped the early lead stand, completing 22-of-30 passes while rushing 12 times for 59 yards for Oklahoma, which has won nine straight regular-season games since last year's 30-13 home loss to then-No. 5 Notre Dame.
"He was really sharp," Oklahoma head coach Bob Stoops said of Bell. "He put the ball where it needed to be, finding the right guys, going through his reads."
Rees finished a woeful 9-of-24 passing for 104 yards, two touchdowns and three interceptions for the Fighting Irish (3-2), who had won nine of the 10 all- time meetings against Oklahoma, with their only other loss to the Sooners coming back in 1956.
George Atkinson III provided the lone bright spot for Notre Dame, rushing for a career-high 148 yards and a score on 14 carries in the setback.
All three of Rees' interceptions came in the first half, with the Sooners turning each one into a touchdown to build a 21-7 lead at the break.
The first came on the third play from scrimmage, as Rees dropped back to pass and was drilled from behind by Eric Striker just as he released the ball. Nelson was there to intercept the pass and return it 24 yards for a score to make it 7-0 less than a minute into the game.
Shannon picked off Rees' next pass and three plays later, Williams tight-roped the right sideline en route to an 11-yard TD for a 14-0 lead just 2:45 in.
"Obviously the interception return and certainly the interceptions in the first half were crucial," Notre Dame head coach Brian Kelly said. "You spot a great team like Oklahoma 14 points, you're putting yourself in a tough situation."
After going three-and-out on its next touch, Notre Dame's offense appeared to find its rhythm, as Tarean Folston ripped off a 36-yard run before Rees hit TJ Jones in the back of the end zone for a 6-yard score to make it 14-7.
Notre Dame moved into Oklahoma territory on each of its next two touches, but neither produced points, with backup quarterback Andrew Hendrix taking a sack on 3rd-and-2 from the OU 38 to thwart the first trek before Rees' third interception of the day ended Notre Dame's next drive.
After Julian Wilson picked off Rees on 3rd-and-10 from the OU 24, Bell converted a pair of third downs to keep OU's ensuing march moving before rolling to his right and firing a cross-field pass into the end zone for Lacoltan Bester, who hauled in the 26-yard score to give Oklahoma a 21-7 cushion with 42 seconds remaining in the half.
Following an OU punt to open the second half, Atkinson brought the Fighting Irish within a score on Notre Dame's first play from scrimmage, bursting through the left side of the line and scampering 80 yards untouched into the end zone to make it 21-14 nearly 2 1/2 minutes into the third.
Michael Hunnicutt hit a 27-yard field goal on Oklahoma's next series before adding a 19-yarder late in the third to give the Sooners a 27-14 lead.
Notre Dame responded with a 7-play, 75-yard march that Rees capped with a 30- yard scoring strike to Troy Niklas on the second play of the fourth quarter, but the Sooners answered with a 75-yard scoring drive of their own to expand the lead.
Facing 3rd-and-3 from the OU 46, Bell fired a quick slant over the middle to Sterling Shepard, who split the safeties and scurried 54 yards into the end zone.
Shepard then hauled in Bell's two-point conversion toss to push the margin to 35-21 with over 12 minutes left in the game.
OU's defense stood tall from there, forcing three straight three-and-outs from the Fighting Irish before Brennan Clay chewed up the final 5:39 off the game clock to secure the victory for the Sooners.