Wade shot 13-of-25 from the floor for the Heat, who snapped a three-game losing streak. Daequan Cook added 14 points, while Shawn Marion had 12 points and 11 rebounds in a winning effort. Mario Chalmers posted 10 points for Miami.
Kobe Bryant had a team-high 28 points for the Lakers, who had won their previous four contests but were held to a season-low point total. Pau Gasol scored 13 points and grabbed 11 rebounds, while Derek Fisher added 13 points in the loss. Jordan Farmer had 12 points for Los Angeles.
The Lakers scored the first seven points of the fourth, as Sasha Vujacic's jumper pulled LA to within 75-70 with 7:52 to play. But Miami kept the Lakers from going on an extended run, as Udonis Haslem's jumper with 2:45 left made it 84-77.
Wade drained two consecutive jumpers around a Gasol dunk, and the Heat led, 88-82, with 1:17 to play. Gasol knocked down a couple free throws on the next possession, and Haslem missed two critical free throws with 54.4 seconds left.
Bryant drove to the lane and hit a spinning jump shot with 41.7 seconds remaining to pull the Lakers within 88-86.
Wade's floater on the ensuing possession was no good, and the Heat rejected two Odom layup attempts with just over 10 seconds to play. Gasol came down with the ball, but Miami knocked it out of bounds to give it back to LA with 9.5 seconds left.
Gasol was fouled just a second later on a layup attempt, but he made only one free throw, leaving the Lakers down a point. Wade was immediately fouled on the inbounds play and made only the second free throw to give Miami an 89-87 lead with 6.8 seconds to go.
Bryant took a jump shot at the buzzer, but the ball rimmed out to give the Heat the victory.
Wade led all players with 12 points in the first, and the Heat and Lakers played to a 26-26 tie in the opening quarter.
Miami closed the half on a 9-2 run, rallying to a 46-46 tie at halftime.
Clinging to a 62-61 lead after Bryant hit a layup with 3:44 left in the third, the Heat finished the quarter on a 13-2 burst, as Wade's three at the buzzer gave the hosts a 75-63 advantage heading into the fourth.