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.