Chris Wilcox scored 20 points, Damien Wilkins had 19 and rookie sensation Kevin Durant finished with 18 as the visiting Seattle SuperSonics beat the Heat 104-95 on Wednesday night to spoil Wade's return.
Seattle never trailed to win for the first time in nine games under new coach P.J. Carlesimo.
Making his first appearance in six months following off-season left knee and left shoulder surgeries, Wade scored 15 points on five-of-nine shooting, along with five assists and three steals in 24 minutes off the bench.
"I'm excited I came out of the game healthy and I've got some things I can build on, but as a team it hurts," Wade said. "I did a lot of things I normally do and did not even think about."
Ricky Davis scored a team-high 19 points for the Heat (1-7), who fell to 0-4 at home for the second time in franchise history.
"We're getting embarrassed," Heat coach Pat Riley said. "We have to simply come together. We're in the abyss right now. It's not much fun."
Elsewhere Boston Celtics 91, New Jersey Nets 69 Kevin Garnett collected 16 points and 11 rebounds as the unbeaten Celtics relied on their defence to move to 7-0. Paul Pierce scored 15 points and Ray Allen finished with 14 for Boston, off to its best start since opening 10-0 in 1972-73.
Richard Jefferson scored 21 points and Jason Kidd had 19 for the Nets, who continue to play without injured All-Star swingman Vince Carter.
LA Lakers 93, Houston Rockets 90 Kobe Bryant scored 30 points and the Lakers took advantage of the second half absence of league top scorer Tracy McGrady to edge the hosting Rockets. McGrady left the game with under a minute left before halftime and was taken to a hospital with a strained right elbow, after hitting Luke Walton's arm trying to knock the ball away.
Trailing 93-90, Rockets centre Yao Ming (26 points and 13 rebounds) intentionally missed a free throw. He grabbed the rebound and passed it to Rafer Alson, whose game-tying three-point try missed as time expired.
Orlando Magic 117, Cleveland Cavaliers 116 (OT) Dwight Howard matched a career-high with 35 points to go along with 16 rebounds as the Magic overcame LeBron James' 14th career triple-double.
James finished with 39 points, 13 rebounds and 14 assists, but with the final seconds ticking off, he was tied up by Hedo Turkoglu on a drive to the basket. On the ensuing play, James tipped the jump ball out of bounds as time expired.
LA Clippers 84, New York Knicks 81 Chris Kaman had 14 points along with 18 rebounds as the Clippers sent the visiting Knicks to their fourth straight loss. Stephon Marbury, fined for missing Tuesday's game, scored 13 points, including a layup with seven seconds left to pull the Knicks within 82-81. But Corey Maggette hit two free throws for the winning margin.
Zach Randolph led the Knicks with 16 points and 19 rebounds.
Minnesota Timberwolves 108, Sacramento Kings 103 Rashad McCants erupted for a career-high 33 points, carrying the Timberwolves (1-5) to their first win of the season. Kevin Martin led the visiting Kings with 22 points and Ron Artest added 17 after serving a seven-game suspension.
Denver Nuggets 110, Portland Trail Blazers 93 Carmelo Anthony scored 25 points and Allen Iverson had 20, leading the Nuggets to their fourth straight win, while ending the Blazers' four-game winning streak.
Utah Jazz 92, Toronto Raptors 88 Carlos Boozer collected 23 points along with 14 rebounds, and Deron Williams scored 22 points, helping the visiting Jazz to their fifth straight victory.
Washington Wizards 103, Indiana Pacers 90 Gilbert Arenas had 30 points and 11 assists as the host Wizards handed the Pacers their fifth straight loss.
New Orleans Hornets 95, Philadelphia 76ers 76 Morris Peterson sank six three-pointers en route to a 27 point effort and the Hornets (7-2) matched their best start in franchise history.
Atlanta Hawks 117, Charlotte Bobcats 109 Joe Johnson poured in a season-high 34 points and the Hawks snapped a two-game slide. Gerald Wallace and Jason Richardson led the Bobcats with 27 points apiece.
Milwaukee Bucks 102, Memphis Grizzlies 99 Michael Redd scored 31 points and Desmond Mason hit a key 15-foot jumper with 13.6 seconds remaining as the host Bucks improved to 3-0 at home. Spain's Pau Gasol led the Grizzlies with 26 points, but missed a three-pointer that would have forced overtime.
Detroit Pistons 111, Golden State Warriors 104 Rasheed Wallace scored 22 points, including 13 in the final frame, as the Pistons overcame a 22-point deficit to keep the Warriors the only winless team in the league. Tayshaun Prince and Richard Hamilton also had 22 points apiece for the visiting Pistons, who were without injured starters Chauncey Billups and Antonio McDyess.
Baron Davis led the Warriors (0-6) with 29 points and 10 assists.