After the champions were surprisingly beaten 1-0 by Athletic Bilbao in their opening match of the season last week, they rebounded in style on Sunday.
Strikes from Carles Perez, Jordi Alba and Arturo Vidal completed a memorable day for the Catalans as they marked defender Gerard Pique's 500th appearance for the club.
Barca, who were without injured forward Lionel Messi, started on the back foot and fell behind when Nabil Fekir netted with a sublime angled strike in the 15th minute.
Griezmann, who joined Barca last month from rivals Atletico Madrid, scored four minutes before half-timeto level the scores.
The French 2018 World Cup winner's maiden goal for the club proved to be the catalyst the Spanish champions needed on the night.
They went on to score four more unanswered goals in 27 second half minutes.
Griezmann curled in from the edge of the box five minutes after the restart, while Perez made it 3-1 after 56 minutes before Alba struck on the hour from close range.
Substitute Vidal then finished off a wonderful team move 13 minutes from the end.
Loren netted a stunning consolation strike from 25 metres for the visitors following an errant pass from Griezmann two minutes later.
Coach Ernesto Valverde was able to bring on academy player Ansu Fati, who at 16 years and 298 days is the second youngest player in FC Barcelona's history, late on.
The Catalans have three points from two La Liga games, while Real Betis have lost both of their games this season.