Samantha Prahalis exploded for a school-record 56.
Tayler Hill added 16 points for Ohio State (23-4, 11-4 Big Ten), which bounced back from Monday's loss at Penn State.
Rachel Banham netted 18 points and Micaella Riche scored 14 points to go with 11 rebounds for Minnesota (14-15, 6-9), which had its two-game winning streak snapped.
Prahalis had 22 points by halftime as the Buckeyes took a 38-26 lead into the locker room.
Two Prahalis free throws with 2:27 left in the game gave the senior 42 points on the night as she passed Katie Smith for Ohio State's single-game points scored record.
Prahalis finished the night 15-of-27 from the floor and 7-of-12 from beyond the arc.