Paul George scored 29 points, C.J. Miles added 21 and Indiana made 16 3-pointers to pull away from Cleveland 123-109.
By winning their third in a row, Indiana stayed a half-game ahead of eighth-place Detroit in the conference standings and pulled three games ahead of idle Chicago, which is trying to fight its way out of the No. 9 slot and into one of the final two playoff spots.
Kyrie Irving led the Cavs with 26 points and six assists, while Kevin Love had 23 points and five rebounds.
Cleveland never seriously challenged after Indiana took control with a 14-0 second-quarter spurt that gave them a 55-41 lead.
Cleveland cut the deficit to nine at halftime and got within 83-74 in the third quarter before the Pacers went on a 13-4 run to extend the lead to 18. The Cavs couldn't get closer than 12 again.
The Cavs face Chicago Saturday and Indiana is at Toronto tomorrow night.