The game was a stark contrast to last week when Northwestern couldn't win in the closing seconds when Siemian slipped attempting a two-point conversion at the end of the game against Michigan.
It might be an even more shocking outcome than the last time the teams met in 1995, when the Wildcats upset the Irish 17-15 in a game dubbed "The Upset of the Century."
But that Northwestern team went to the Rose Bowl. This year's Wildcats had lost four straight and were floundering offensively.
Both teams turned the ball over four times in a sloppy game. Notre Dame's final turnover occurred with 1:28 when the Irish (7-3) were trying to run out the clock and the usually reliable Cam McDaniel fumbled at the Northwestern 33-yard line when he was stripped by safety Ibraheim Campbell and it was recovered by linebacker Jimmy Hall.
Northwestern (4-6), which had minus 9 yards rushing last week against Michigan, rushed for 263 yards and had 547 yards of total offense, both season highs. All four of Mitchell's field goals were longer than his previous career high of 29 yards.
The Irish defense struggled as it gave up 30 or more points for a fifth straight game, only the second time that's happened. The other time was in the first five games of 2007, when the Irish finished 3-9 in one of the worst season's in Notre Dame history.
Justin Jackson led Northwestern with 149 yards and a touchdown. Siemian was 30 of 48 passing with two interceptions for 284 yards and a touchdown. Kyle Prater had 10 catches for 81 yards and a touchdown.
Everett Golson threw three touchdown passes to Will Fuller and scored on a 61-yard run, but he also threw an interception and has a fumble. He has 19 turnovers in the past seven games. Tarean Folston rushed for 106 yards.
Mistakes almost kept Northwestern from having a chance to win. Siemian was intercepted in the end zone by nickel back Matthias Farley late in the second quarter and the Wildcats had at least a half dozen dropped passes, including three by Tony Jones that appeared to be sure touchdowns. Notre Dame safety Austin Collinsworth, who hadn't played in a month because of a shoulder injury, picked up a fumble by Garret Dickerson and returned it 32 yards for a touchdown.
The Wildcats also surrendered a 33-yard pass by Golson on a third-and-24 and Jackson fumbled following a 19-yard gain.
But it was the Irish who couldn't overcome their mistakes, including the four turnovers. Kyle Brindza missed a pair of field goals, including a 42-yard attempt in overtime.
The Irish had several other costly miscues, including backup quarterback Malik Zaire bobbling a snap on an extra point. The kick was blocked by cornerback Nick VanHoose, who picked up the loose ball and returned it for a two-point conversion. Zaire was holding for the first time after walk-on Hunter Smith had his third bobble snap last week against Arizona State.