Tettleton scampered in from a yard out to take a 17-14 lead almost seven minutes later.
Tettleton finished 31 of 41 passing for 324 yards and two scores, and added 47 yards and a score on nine carries on the ground. Beau Blankenship had 109 yards on 31 carries.
Penn State's front seven — thought to be the strength of the team — got dented by Ohio's fast-paced offense. Warm, humid conditions also seemed to tire players, and cornerback Stephon Morris later left with an ankle injury.
"I think the line was able to take control of the game. I think we wore them down a little bit," Solich said. "I think maybe our pace took a toll and did help us in the game."
Freshmen and other new faces played key roles all over the field for Penn State, necessitated in part by some transfers following the NCAA sanctions and other offseason departures.
A huge cheer erupted after freshman linebacker Nyeem Wartman burst up the middle to block an Ohio punt that Penn State recovered at the Bobcats 18. Wartman was one of four freshmen to debut Saturday.
Three plays later, junior tight end Matt Lehman, playing his first game, nearly lost his footing along the sideline before bursting into the end zone for a 14-yard score and a 14-3 lead.
An offense that used a lot of no-huddle looked OK without 1,200-rusher Silas Redd and receiver Justin Brown, who elected to transfer following the NCAA penalties.
But McGloin and the offense went scoreless after halftime and second-half defense hurt Penn State. A missed tackle by safety Malcolm Willis helped Smith get free for a 31-yard gain to the Penn State 5 on third-and-2 with less than four minutes left, one of several key third-down conversations for the Bobcats.
Tettleton's 5-yard touchdown pass to Donte Foster in the corner of the end zone with 2:55 left put an exclamation point on Ohio's first win over a Big Ten opponent since a 20-17 victory over Illinois in 2006.
Ohio returned eight starters on defense, while Tettleton is one of the MAC's top quarterbacks after setting 12 new school records last season.