The Heat sealed the best-of-seven semi-final series 4-2 and will face Boston or Philadelphia for the conference title. The Celtics and 76ers play a deciding Game Seven on Saturday.
Miami return to the Eastern finals for the second successive year. Last season they beat Chicago to reach the NBA Championship where they lost to the Dallas Mavericks 4-2.
Indiana made a strong start and led 28-21 after the first quarter before Wade took charge, scoring 20 points in the second. Wade ended with 41 points, 10 rebounds and three assists, while LeBron James had 28 points.
Game Five in Miami had been a brutal affair with some nasty fouls, but while no quarter was given on Thursday the aggression was kept within acceptable limits.
"It was a tough, physical, very competitive series and we hope that the series will not be marred by the last game because if you take that out, it was just a competitive, hotly contested series and that is what it should be remembered for," said Miami head coach Erik Spoelstra.
Miami, who wrapped up the series with three consecutive wins, were helped by 22 Indiana turnovers, compared with the Heat's 10, and solid performances from Mario Chalmers (15 points) and Mike Miller (12).
Miami were playing without suspended Udonis Haslem and the injured Chris Bosh, but the form of Wade, who had 26 points in the first half to equal the franchise postseason record for the opening two quarters, more than compensated.
David West top scored for Indiana with 24 points while Danny Granger, who shrugged off an ankle problem to play, had 15 and George Hill 18.
The absence of Bosh, who picked up an abdominal injury in Game One, caused Miami some problems in the series as they were forced to adjust their offense but Indiana coach Frank Vogel said it had not seriously weakened the Heat.
"Chris Bosh is an awesome basketball player but when he goes down ... that means more touches for LeBron and Wade, that's not an advantage," he said.
"I think we could have beaten these guys if we had played our best but we didn't play our best.
"Hopefully we'll be back to see these guys in the future but you have to tip your cap to Miami, coach Spoelstra did a great job," he added.