Dwight Howard had 29 points and 20 rebounds, Hedo Turkoglu capped his 22-point night by hitting a huge 3-pointer with 11 seconds left and the Magic survived some late-game Miami heroics to beat the Heat 121-114 on Friday night.
Wade matched a career high with 48 points, 20 of them coming in the fourth quarter and all of them in regulation for Miami, which fell to 8-22.
Daequan Cook sent the game to overtime with a long 3-pointer with 1.9 seconds left in regulation, then tied the game again on another 3 with 1:18 left for Miami. But Turkoglu scored the next five points, sealing Orlando's seventh straight win in the series between the Sunshine State rivals.
Rashard Lewis scored 17 points, while Keith Bogans and Carlos Arroyo each had 13 for Orlando. Keyon Dooling and Maurice Evans finished with 10 apiece for the Magic.
Ricky Davis and Udonis Haslem each scored 17 for Miami, which played without starting center Shaquille O'Neal and point guard Jason Williams. Dorell Wright scored 14 points and Cook finished with 11 for the Heat.
Orlando led 84-79 after Evans' three-point play with 9:52 left, a score set up by a turnover by Wade.
So he went to work, as if to make up for the mistake.
He scored eight straight points to stake Miami to an 87-84 lead and, after Lewis made a free throw following a technical against Haslem, Wade found Wright for a dunk that gave Miami a four-point lead.
Cook then added a 3-pointer, putting Miami ahead 92-85 and capping a 13-1, 3 1/2-minute run.
Orlando wasn't fazed. Lewis made a 3-pointer, Howard added a three-point play 41 seconds later, and suddenly the Magic were within 92-91.
But Wade, who was only off the floor for 1:25 of the first half, had enough legs for one last push.
He made back-to-back jumpers to give Miami a 98-91 lead with 3:40 to play, and from there the only question was whether the Heat would be able to survive one more Orlando run.
