Blake Bell threw a 54-yard touchdown pass to Sterling Shepard in the fourth quarter and No. 14 Oklahoma beat No. 22 Notre Dame 35-21 on Saturday.
It was the Sooners' second win over the Fighting Irish in 11 tries.
The Sooners had three interceptions that led to TDs, including a 24-yard score by linebacker Corey Nelson.
Damien Williams added an 11-yard TD run after an interception by linebacker Frank Shannon and Bell threw a 26-yard TD pass to Lacoltan Bester to cap an 88-yard drive after an interception by cornerback Julian Wilson.
The Irish cut the lead to 27-21 in the fourth quarter, but the Sooners answered with Shepard's TD.
The only other victory for Oklahoma (4-0) in the series was a 40-0 win in 1956 that remains the worst home loss for the Irish (3-2).