It was San Antonio's fifth road game in eight days and the Spurs have won them all while boosting the NBA's best record to 13-3. San Antonio will conclude its grueling trip with a game in Miami on Thursday.
The Spurs have lost just one of their 10 road games this season.
San Antonio closed the first period on a 19-4 run to take command and held the Magic scoreless during a 3-minute stretch early in the second half while building an 18-point lead.
Ginobili made 6-of-9 from the field as part of the Spurs' 53-percent shooting effort. Gary Neal added 19 points and Tim Duncan had 15 for San Antonio, which also has wins over Boston, Indiana, Toronto and Washington on its current trip.
Arron Afflalo scored 16 points to pace Orlando, which has dropped its last two games.