Siemian, who was 21 of 37, and the Wildcats (2-2, 1-0) established control early with short passes and ball-control offense that netted 361 yards.
Northwestern's defense held Penn State (4-1, 1-1) to 50 rushing yards and just 266 overall, pressuring Penn State quarterback Christian Hackenberg all game.
The Wildcats led 14-6 and broke the game open in the fourth when linebacker Anthony Walker intercepted Hackenberg and returned it 49 yards for a score.
Northwestern's Matthew Harris was carted off late in the third after a collision with Hackenberg. Harris was responsive and offered the thumbs-up signal while leaving the field.
Any mistake the Wildcats made on offense or special teams to give Penn State a chance at gaining momentum was quickly corrected by their defense.
The Wildcats limited Penn State to 18 rushing yards through three quarters, including nine carries from by Hackenberg who was pressured up the middle the entire game.
The Wildcats' Jack Mitchell missed a 44-yard field goal on their first possession but dominated the rest of the half by rolling up 232 yards, 202 in the air.
Northwestern's two first quarter touchdowns marked the first points scored against Penn State in the first quarter this season. Northwestern totaled just seven points in the opening quarter in its three previous games.
Penn State dodged two bullets when Northwestern's Christian Salem, the team's holder on field goals, was stopped short of the goal line on a fake field goal attempt, and a fumble returned for a touchdown by Matt Harris was ruled an incomplete pass after review.
Ficken booted a 42-yard field goal with five seconds left in the half.