The Bobcats quarterback threw for 324 yards and two touchdowns, completing 31-of-41 passes in the season opener for both teams and the first game for new Nittany Lions Coach Bill O'Brien, who took over after Joe Paterno was fired in the wake of the revelations about his longtime assistant, who was convicted of sexually abusing several boys over a period of years.
Tettleton also ran nine times for 47 yards and a touchdown.
The Bobcats' attack was balanced by Beau Blankenship, who rushed 31 times for 109 yards and caught seven passes for 72 yards.
Matt McGloin completed 27-of-48 passes for 260 yards and two touchdowns and one interception.
Bill Belton had 13 carries for 53 yards as he took over at running back after Silas Redd (1,241 yards and seven touchdowns in 2011) to transferred to Southern California.
The Nittany Lions, who hadn't opened a season with a loss since 2001, are facing four years in which they are ineligible to play in a bowl game. The school also was saddled with a $60 million fine by the NCAA, which stripped the program of all its 111 wins between 1998 and 2011.
O'Brien, a former New England Patriots coach, is the 15th head coach in PSU history.
Paterno, 85, died of lung cancer in January. Paterno had been the all-time winningest coach in FBS history before the scandal.