George Hill provided a three-point play with 46.5 seconds left to give the Pacers their first lead at 93-92 following a 17-0 fourth-quarter run.
After Kyrie Irving's free throws put the Cavaliers back on top, George sank the decisive shot from left corner for a 96-94 Indiana advantage.
The Pacers then went on to close out the win, outscoring Cleveland 35-10 in the final frame.
Hill ended with 29 points for Indiana, which holds the third seed in the Eastern Conference.
Irving topped the Cavaliers with 29 points and seven assists.
Putin thinks Obama would save him if he were drowning
Justin Bieber crashes Drake Bell's album release party