The game was close through three quarters until George connected on a 3-pointer at the end of the third and Luis Scola began the fourth with another basket, sparking a 14-1 run that put the Pacers firmly in front.
Lance Stephenson provided 19 points, seven rebounds and five assists for Indiana, which reached last season's Eastern Conference Finals before losing to the eventual NBA champions Miami Heat in seven games.
Andrew Nicholson came off the bench for 18 points on 8-of-10 shooting for the Magic, who finished last season with the NBA's worst record (20-62).
No. 2 overall draft pick Victor Oladipo netted 12 points in his professional debut.