The unbeaten Buckeyes (9-0, 5-0 Big Ten) scored virtually at will while racking up 640 yards of total offense to 116 for Purdue (1-7, 0-4).
Kenny Guiton came off the bench to add another scoring throw and a pair of running touchdowns, and Carlos Hyde gained 111 yards on the ground for Ohio State.
Doran Grant opened the scoring in the first quarter by returning an interception 33 yards for a touchdown.
Danny Etling was 13-of-29 for 89 yards and an interception for the Boilermakers. Akeem Hunt was Purdue's leading rusher on the long day with 23 yards on six tries.