The Cavs led by one point at halftime, but the Pacers used a decisive third quarter, during which they outscored Cleveland by 10, to pull away.
Six Indiana players scored in double figures. Roy Hibbert had 18 points, Lance Stephenson had 16 points, David West scored 15 points, George Hill scored 13 points, Paul George scored 10 points and Gerald Green scored 14 off the bench.
The Cavs also had six players score in double figures, but the team shot just 40 percent while Indiana made 49 percent of its shots.
Kyrie Irving had 17 points and five assists, but also turned the ball over six times. Tristan Thompson and Tyler Zeller each scored 12 points and Alonzo Gee and Dion Waiters each scored 11 points. C.J. Miles scored 10 points off the bench. Thompson also grabbed 13 rebounds.
Kyrie Irving and the Cleveland Cavaliers (5-22) have dropped five straight games, but will look to end that streak Friday night against the Indiana Pacers. On Saturday they will tip off against the Milwaukee Bucks.