Miami had lost five straight games and came into the contest with a 1-9 record against the five teams that have a better record than it does. In a physical, defensive battle, however, Miami made the plays down the stretch to halt the Lakers' winning streak at eight games.
Miami had no more than a two-point lead during the final 7:30 until Wade made a layup that put the Heat in front 92-88.
Kobe Bryant then turned the ball over for the Lakers and, after Los Angeles regained possession, missed a 3-point try.
LeBron James added two free throws for Miami to close out the scoring with 19 seconds to play.
Chris Bosh led Miami with 24 points, Wade had 20 and James had 19 while making 7-of-17 shots from the field.
Miami shot 45 percent and the Lakers hit 40 percent. Miami won the rebounding duel by nine.
Bryant scored 24 points, but hit just 8-of-21 shots. Pau Gasol added 20 points.
Miami does not own a win this year over Boston, Chicago, San Antonio or Dallas, but the Heat swept their season series with the Lakers. They downed the Lakers in Los Angeles by 16 points on Christmas Day.