Ohio State called the game off when further positive COVID-19 tests came back after PCR testing Friday afternoon. Head coach Ryan Day tested positive for the virus earlier in the day.
"We have continued to experience an increase in positive tests over the course of this week," Ohio State athletic director Gene Smith said in a statement. "The health, safety, and well-being of our student-athlete(s) (are) our main concern, and our decisions on their welfare will continue to be guided by our medical staff."
The positive cases could have a substantial effect on a program that has national title hopes. Under the Big Ten's COVID-19 protocols, the earliest a player can return to game action after a positive diagnosis is 21 days.
The conference also mandates that teams must play at least six games in order to play for the Big Ten title.
The 4-0 Buckeyes, who've already had two games canceled, have contests against Michigan State and Michigan left on their schedule.
However, if the average number of Big Ten games played drops below six, schools must play no less than two fewer contests than the average to qualify for the conference championship game.