Miami won its sixth in a row, fighting off a Los Angeles comeback with their three big stars sharing the spotlight.
The Lakers held a one-point lead early in the fourth period, but the Heat built as much as a nine-point advantage down the stretch.
Miami's lead was five points when the Heat's Mario Chalmers missed a jumper with 1:15 to play. Chalmers then grabbed the rebound of his own miss and Wade quickly followed by a reverse layup that all but clinched the game with 57 seconds remaining.
Miami played the opener of a four-game road trip that will continue with stops in Sacramento, Portland and Denver.
The Lakers lost their third in a row and slipped to 7-7 at home.
Nick Young hit four 3-pointers and led Los Angeles with 20 points. Miami attempted just one more shot from the field than did the Lakers, but made eight more while shooting 51 percent.
Swim Week Miami Beach 2014 [PHOTOS]