Willie Green finished with 14 points and Thaddeus Young 11 as the Sixers won for the fourth time in six games.
The Heat, playing their second game since center Shaquille O'Neal was dealt to the Phoenix Suns, struggled throughout and lost their sixth straight.
Dwyane Wade scored 19 points on 5-for-17 shooting, Jason Williams added 14 and Dorell Wright 16 for Miami, which is stuck on nine wins. The Heat have lost 21 of their last 22.
The Sixers held a three-point lead heading into the fourth quarter and used a 12-3 run to break the game open. During Philadelphia's run, Miami endured a game-deciding 1-for-11 shooting slump.
It was the second losing effort in two days for Miami and came just over 24 hours after the Heat sent O'Neal to Phoenix in a blockbuster deal that netted the Heat Shawn Marion and Marcus Banks.
But Marion, a four-time All-Star and Banks weren't in the lineup, and the Heat fielded a nine-player lineup for their second straight game.
Miami was down to eight players in the second half after losing Alexander Johnson to an ankle injury with just over seven minutes left in the second period.
