Trevor Siemian threw for 165 yards, including a 41-yard pass to Dan Vitale that helped set up the winning kick. The Wildcats (8-3, 4-3 Big Ten) then forced a punt near midfield, and by the time Michigan State (5-6, 2-5) got the ball back at its own 20, there was only 1:29 left.
Northwestern lost fourth-quarter leads in gut-wrenching losses to Penn State, Nebraska and Michigan, but this time Michigan State's Andrew Maxwell threw four straight incompletions to seal the Spartans' fate.
All seven of Michigan State's conference games have been decided by four points or fewer.
It was Northwestern's first win over Michigan State since 2007, and the Spartans must now beat Minnesota next weekend to become bowl eligible.
The Wildcats spoiled Michigan State's home finale despite what was announced as an upper extremity injury to running back Venric Mark, who didn't play in the second half. Siemian and Kain Colter split time at quarterback for the Wildcats. Colter went 13 of 20 for 81 yards and a touchdown.
Northwestern led 13-5 early in the third quarter after David Nwabuisi returned an interception 43 yards for a touchdown. Maxwell seemed shaken up on the play, but he was able to keep playing and quickly led the Spartans on a sharp 65-yard drive that ended with his 15-yard scoring pass to Aaron Burbridge. A 2-point conversion pass to Keith Mumphery tied it at 13.
Michigan State lost the ball twice inside the Northwestern 5-yard line in the first half. A fumble on the snap gave the Wildcats the ball at their own 2 late in the first quarter, but Colter was hit in the end zone by Max Bullough and William Gholston for a safety that made it 3-2.
Michigan State led 5-3 in the second and had the ball at the Northwestern 1, but star running back Le'Veon Bell was dropped for a loss of 3 on fourth down.
The Wildcats took a 6-5 lead into halftime when Budzien made a 43-yard field goal in the final minute of the quarter, and Michigan State's Dan Conroy missed from 37 at the other end.
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