Kenny Pickett threw a touchdown pass and ran for another, as Pitt scored on each of its first six possessions in its season opener at Heinz Field.
Seven Panthers players were held out of the game due to COVID-19 protocols.
Pickett and offensive coordinator Mark Whipple spread the love around as Pickett threw to seven receivers and six players scored touchdowns during the Panthers' offensive outburst.
A Paris Ford interception set up Pitt's first score, a 1-yard Daniel Carter plunge. Pickett connected with Shocky Jacques-Louis on a 68-yard strike before scrambling into the end zone from six yards out to score on Pitt's second drive. He then connected with wide-open Maryland transfer DJ Turner for a 51-yard score.
After that, Whipple turned over the offense to the running game, with Vincent Davis scoring on a one-yard rush, Israel Abanikanda scampering to pay dirt on a 10-yard draw and Todd Sibley Jr. plunging in from one yard out on Pitt's three second-quarter possessions.
Pickett finished 14-of-20 for 277 yards. Freshman Jordan Addison was his most frequent target, hauling in seven catches for 35 yards.
The Pitt defense pitched its first shutout since 2014, holding the Governors to 146 yards of total offense and 10 yards rushing.
Pitt was favored at minus-30 to win the game, but bets placed on the event will be refunded because the second half was cut short. According to Las Vegas sportsbook rules, 55 minutes must be played in order for a game to have action.
The Associated Press contributed to this report.