With their senior point guard leading the way, the Buckeyes (20-1, 7-1) left Bloomington with a 73-55 victory.
Prahalis scored her first field goal more than 15 minutes into the game, but it came in the midst of a 13-6 run that saw Ohio State cut what had been an eight-point deficit to one (26-25) heading into the locker room.
She had six points and an assists as the Buckeyes began their comeback, and she picked up right where she left off after intermission.
Prahalis opened the second half scoring with a jumper that gave Ohio State its first lead since the opening minute of the game, and she was just getting warmed up. She added a free throw a minute later then assisted on consecutive baskets by center Ashley Adams and power forward Darryce Moore.
Prahalis followed with another jumper, then backcourt-mate Tayler Hill got into the action with a pair of baskets – her first two of the game – to push the Buckeyes' lead to 38-26.
All told, Ohio State scored the first 13 points in the second half to take control of the game.
Indiana would never recover. The last-place Hoosiers (5-16, 0-8) trailed by as many as 24 while succumbing to the superior athleticism and size of the ninth-ranked Buckeyes, who also got an exemplary performance from Adams, their 6-5 sophomore center.
Adams scored 15 points, grabbed 12 rebounds and blocked five shots.
Prahalis and Hill finished with 18 points apiece, all of them coming in the last 25 minutes of the game.
Hill, the Big Ten's leading scorer entering the game, went 0 for 5 from the field in the first half but made 7 of 10 after intermission.
Prahalis added nine assists, five rebounds and three steals in addition to her scoring.
Aulani Sinclair led Indiana with 27 points. She made 5 of 7 three-pointers and added six rebounds in defeat.
Ohio State shot 60 percent (18 for 30) in the second half while holding the hosts to 28.2 (11 for 39).