His second pick-off of Tommy Rees led to James Conner's go-ahead, 1-yard touchdown run with 9:36 remaining.
The Panthers (5-4) then used a tough defense to stymie the Fighting Irish on two final possessions.
Conner finished with two touchdowns and Tom Savage completed 23-of-35 passes for 243 yards and two scoring strikes to Devin Street for Pittsburgh.
Rees went 18-of-38 for 318 passing yards, two touchdowns with two key interceptions for Notre Dame (7-3), which had its four-game winning streak snapped.
T.J. Jones scored twice but lost a fumble for the Irish, whose chances of landing a BCS bowl berth were extinguished.
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