Hamilton teamed with quarterback Trace McSorley on the first two scoring passes and caught the third from running back Saquon Barkley to cap the scoring in the fourth quarter. Hamilton hauled in his 180th career catch midway through the fourth quarter to break the record set by Deon Butler in 2008.
Barkley returned the opening kickoff 98 yards for a touchdown and finished with 221 yards to pad his Heisman Trophy resume. Penn State (5-0, 2-0 Big Ten) turned two first-quarter turnovers into touchdowns to spark the rout. McSorley added a rushing touchdown, Nick Scott scored on a fumble return, and Tyler Davis added a pair of field goals for Penn State.
The Hoosiers (2-2, 0-2) turned the ball over on their second play of the game when Morgan Ellison coughed it up to linebacker Jason Cabinda after an 18-yard gain. McSorley capped an ensuing six-play, 39-yard drive with a 1-yard touchdown run.
Indiana fumbled it away again when Irvin Charles ripped the ball out of punt returner J-Shun Harris' hands. Scott scooped it up and returned it 13 yards to put Penn State up 21-0 less than 10 minutes in.
On his team's next possession, Barkley made a pretty one-handed catch well behind the line of scrimmage that he turned into a 36-yard gain. It set up McSorley's 8-yard touchdown pass to Hamilton, who made a nice adjustment on the catch over a defender four plays later.
But Penn State, wearing white cleats and throwback jerseys that blended design elements from past teams, went quiet in the second quarter.
The Hoosiers found some momentum with a quarterback change. Peyton Ramsey relieved an ineffective Richard Lagow and led two scoring drives.
Ricky Brookins scored on a 2-yard run late and Simmie Cobbs caught an 18-yard scoring pass from Ramsey to cut Penn State's lead to 28-14 before halftime.
Ramsey was 8 of 17 for 78 yards with an interception and added 53 yards on 12 carries.