Gagne and Petrucci went to the Alabama track split by just four points at the head of the standings, but a 12th win of the season in Saturday's opener and a second-place finish in Sunday's curtain-closer proved enough for the American rider was enough to defend his crown.
Warhorse HSBK Ducati rider Petrucci on the other hand finished fourth in the first race after being handed a five-second penalty for jumping a start, although this was subsequently overturned, promoting him to third.
The Italian could do no more than fourth in the second race, won by Gagne's Attack Performance Yamaha teammate Cameron Petersen, leaving him 20 points adrift in the final reckoning.
"It was amazing being able to race with Danilo," said Gagne. "That guy is a world-class racer. I don’t think there has ever been anybody that I wanted to beat more, just because of his resume. He’s a MotoGP guy, a MotoGP winner.
"I don’t know how many of those we’ve had here in the States, so I wanted to do right and protect the home turf here and bring this MotoAmerica championship home with an American.”
Moving to MotoAmerica after losing his KTM MotoGP ride, Petrucci got his season off to the ideal start with three wins in the first three races, taking a double win at the Circuit of the Americas and another at Road Atlanta.
The 31-year-old would only add two more triumphs to his tally for the rest of the year, but proved his consistency with 16 podiums in 20 races.
Gagne on the other hand would go on to take 12 wins, but wasn't as consistent, with his higher rate of DNFs - three to Petrucci's one - keeping the title race tigher than it would have been otherwise.
Petersen and Matthew Scholtz (Westby Yamaha) were the only other race winners all season, ending up third and fourth in the final standings ahead of another ex-MotoGP racer, Hector Barbera (Tytlers BMW).
Having wrapped up the MotoAmerica title, Gagne and his Attack Performance Yamaha team will now turn their focus to their upcoming World Superbike wildcard appearance at Portimao, which has been viewed as a possible precursor to a step up to the world stage on a full-time basis in 2023.
Petrucci was also linked to a wildcard at Portugal earlier in the season amid rumours he could be in line for a WSBK move with Ducati, but no confirmation has been forthcoming.
Last week, Ducati finally confirmed that Michael Ruben Rinaldi will be staying as Alvaro Bautista's teammate in 2023, ending speculation that Petrucci could replace the younger Italian at the works team.
One rider tipped to be moving back to MotoAmerica next year is five-time series champion Cameron Beaubier. The Californian has announced he will be leaving Moto2, where he has raced since last year, at the end of 2022.
