Northwestern quarterback Kain Colter threw for a career-high three touchdowns and the Wildcats (9-3, 5-3 Big Ten) reached nine victories for the first time since 2008.
Penalties and turnovers hurt Illinois (2-10, 0-8), which has lost nine straight and 14 in a row in Big Ten play. The Illini committed four turnovers -- including three interceptions -- and eight penalties in their season finale.
Northwestern captured the Land of Lincoln Trophy after losing to the Illini in the rivalry game the last two seasons.
Donovonn Young rushed for 74 yards and a touchdown for Illinois, which ranks last in the Big Ten in scoring offense in coach Tim Beckman's first season. Nathan Scheelhaase went 9 for 14 for 91 yards and two interceptions.