With the Heat missing Chris Bosh due to a strained abdominal muscle, the defending Eastern Conference champions shot only 37 percent from the field and managed a mere 32 points in the second half while fading away.
Indiana grabbed a 2-1 advantage in the Eastern Conference semifinals and will try to take complete control of the series when it hosts Game 4 Sunday.
The Pacers scored the game's first seven points, fell behind by nine after one quarter and then rallied to tie the score at halftime.
It was still tied game 2 minutes deep into the third quarter, but the Pacers outscored Miami 28-11 over the next 12:20. Granger had nine points during that run and Collison delivered all seven of his points.
In addition to shutting down the Heat from the field, Indiana claimed 16 more rebounds than did Miami.
Four of the Indiana starters reached double figures in scoring with George Hill producing 20 points. Roy Hibbert scored 19 and had 19 rebounds while Granger added 17 points and David West 14.
Wade averaged 22.1 points a game during the regular season and had been averaging 22.6 in the playoffs.