Paul George, under heavy pressure from LeBron James, missed a 3-point try with 11 seconds left that would have tied the game.
It was the second meeting this year between the top two teams in the Eastern Conference and they each have produced a home victory. They will not meet again until March.
Wade made 15-of-25 shots from the field while James had 24 points and nine rebounds. James' appearance had been questionable due to an ankle injury suffered earlier this week.
George led the Pacers with 25 points and David West added 23.
Indiana still owns the best record in the East at 20-5, but Miami moved within a game of the Pacers.