The Heat trailed for much of the game before putting on a surge late in the third period to get in front. Their lead grew to nine by the midway point of the final quarter and they held on to win their third in a row.
Wade finished with 29 points and seven assists and LeBron James added 18 points with six assists and five rebounds.
The Heat shot 53 percent from the field with Wade going 13-of-23.
Blake Griffin led the Clippers with 27 points and 14 rebounds. Los Angeles has lost two in a row after winning three straight. The consecutive losses have come in the first two outings of a three-game road trip that concludes on Saturday in Houston.