Rashard Mendenhall rushed for 76 yards and a touchdown on 18 carries for Illinois (4-1, 2-0 Big Ten), which beat a ranked opponent for the first time in six years.
Quarterback Juice Williams completed 11-of-24 passes for 120 yards, with a touchdown and two interceptions, and also ran for 37 yards before he was replaced by Eddie McGee -- who threw three incomplete passes but had a 53-yard run in the fourth quarter.
Penn State's Anthony Morelli passed for 298 yards and a touchdown but threw three second-half interceptions.
Austin Scott rushed for 52 yards and a touchdown and Rodney Kinlaw added 66 yards on the ground for the Nittany Lions (3-2. 0-2).