Ohio (3-2) beat a major-conference team for the first time since 2000, when the Bobcats beat Minnesota. Ohio, a member of the Mid-American Conference, also beat Maryland in 1997, but otherwise hadn't defeated a major-conference foe since a 1973 win over Northwestern.
Kentucky (1-3) hadn't lost to such a lightly regarded opponent since 1994, when it fell to Northeast Louisiana during a 1-10 season. Kentucky beat Ohio 35-14 last year.
Ohio led 14-10 at halftime and forced five Kentucky turnovers in the second half, one as the Wildcats appeared poised to take the lead. Still trailing 14-10, Kentucky had reached the Ohio 10 early in the fourth quarter when linebacker Matt Muncy intercepted a pass from Shane Boyd.
Four plays later, Ohio quarterback Austen Everson threw a slant pass to Mayle, who broke a tackle and completed the 89-yard scoring play, the second-longest pass in Ohio history.
With more than eight minutes remaining, Kentucky went for it on fourth-and-13 from its own 35 on its next series, and when Boyd's deep pass eluded the grasp of Scott Mitchell, Ohio had prime field position. Kalvin McRae scored on a 12-yard run to seal the win for the Bobcats.
Mayle finished with four catches for a career-high 157 yards, one week after he had five catches for 134 yards in a 34-0 win over Buffalo. Mayle's yardage total was the best by an Ohio receiver in 11 seasons.
Mayle also led Ohio in rushing, finishing with 52 yards on five carries, all on end-around plays