Jason Williams added 20 points and eight assists for the Heat, who led 91-75 with 8:05 left before the Pacers - who had only 10 players in uniform - got within two by going on a 23-9 run.
But Wade hit a pair of free throws with 24.5 seconds left, then drove full-court for the winning score.
Danny Granger had a career-high 28 points on 9 of 13 shooting for Indiana, but came up short on a potential game-tying 3-point try as the final buzzer sounded.
The Pacers acquired Troy Murphy, Mike Dunleavy, Ike Diogu and Keith McLeod from the Warriors for Stephen Jackson, Sarunas Jasikevicius, Josh Powell and Al Harrington, but none of the new players were available Thursday.
Marquis Daniels had a season-high 21 for the Pacers, who got 17 points and 10 rebounds from Jermaine O'Neal.
The Heat were playing without Shaquille O'Neal for the 32nd consecutive game while he continues his recovery from knee surgery - he will not play in Philadelphia on Friday, either, but his return is expected soon.
Alonzo Mourning had 14 points and Jason Kapono had 11.