The Cavs suffered their first loss in round one for eight years, a valiant rally in the second half not enough to overtake the on-point Pacers.
On top from the start, Indiana eventually led by 23 by the third quarter, with racking up 32 points.
LeBron James scored 24, with 12 assists and 10 rebounds and Cleveland came within seven points of the visitors, although Indiana pulled away to convincingly secure game one.
Former Indiana star Paul George scored 36, including a franchise play-off record of eight three-pointers, as the Oklahoma City Thunder held the Utah Jazz at bay to take their Western Conference opener 116-108.
A new arrival at OKC this season, George had eight of 11 long-range shots on-target and smashed the Thunder’s previous three-pointer playoff record of five.
The Houston Rockets edged out the Minnesota Timberwolves 104-101 in the opening round of their Western Conference play-off series.
James Harden provided the power in a fourth-quarter surge that saw him notch up 13 points, bringing his total to 44.
The effort helped Houston keep the Timberwolves from the door – the visitors coming to within three points in the last minute of the game.
Back in the Eastern Conference and the Boston Celtics were victorious in their opener with the Milwaukee Bucks, beating them 113-107 in overtime.
Kris Middleton beat the buzzer to level for the visitors and take the score 99-99, but in the end it was Al Horford and company’s night.
He scored 24 points and had 12 rebounds and three blocks, while team-mate Terry Rozier added 23 points, four rebounds and three assists on top.