Wade led all scorers and drilled a jump shot in traffic with 0.1 seconds to play after failing to get a foul call when he pump-faked Paul George and then leaned into the contact.
LeBron James scored 27 points and had eight rebounds for the Heat. He drained a 3-pointer on the final play in regulation to tie the score and send the game into overtime.
James' shot was one only three treys the Heat made in 13 attempts.
The Pacers shot 37.9 percent from the field to 46.7 percent for Miami.