Goran Dragic added 20 points and James Johnson had 18 as the Heat evened the best-of-seven playoff series. Josh Richardson contributed 14 points and Wayne Ellington and Kelly Olynyk each had 11.
Game 3 will be Thursday in Miami.
"This is more like it to be going back home 1-1," Wade said. "I like the way we came back from that first one. ... Tonight was just about being on the attack."
Ben Simmons led the Sixers with 24 points, and he added nine rebounds and eight assists. Dario Saric had 23 points and nine rebounds. Marco Belinelli scored 16 points while Ersan Ilyasova scored 14 points and grabbed 11 rebounds. JJ Redick had 11 points on just 4-for-13 shooting.
The Sixers won their final 16 regular-season games and the first game of the series, and they hadn't sustained a loss since March 13.
Philadelphia was 7 of 36 from 3-point territory and shot just 41.7 percent overall in playing their second straight playoff game without injured center Joel Embiid.
"That's kind of who we are," Sixers coach Brett Brown said. "Some of our guys had a rough night. It's been sort of who we are. Without Joel, you cater to the team's strengths. If you're seeking to become a whole team, you need Joel Embiid."
The Heat scored five quick points to open the fourth, going up 91-75 just 56 seconds in.
A 10-2 surge by the Sixers capped with a 3-pointer by Saric got Philadelphia within 93-85 with 8:58 remaining. On the 76ers' next possession, Simmons finished a fastbreak with a dunk, and the Heat's lead was sliced to 93-87.
Johnson responded by hitting a huge 3-pointer to put the Heat up 96-87.
When Saric later drove to the basket and scored, the Sixers trailed only 96-92 with 5:47 left.
After re-entering the game, Wade had a steal and dunk with 4:04 left to give the Heat a 100-96 lead. Wade then found Johnson for a dunk and a 102-96 advantage. Dragic eventually capped a 6-0 run with a baseline jumper for a 104-96 lead with 2:25 left, and the 76ers never challenged again.
"There's a way you have to play in the NBA playoffs from a toughness standpoint, from a physicality standpoint, that was shown tonight," Brown said. "There's a spirit in the way they played tonight -- it was desperate -- that is most on my mind going down to Miami."
The Sixers had surged to a 29-22 lead at the end of the first quarter. Then the Heat turned into a completely different team with a dominating second quarter, a 34-13 outburst that turned a seven-point deficit into a 56-42 advantage at halftime.
Wade was scintillating off the Miami bench with 21 first-half points on 8-of-9 shooting. After scoring his 17th point, Wade moved past Boston Celtics legend Larry Bird for sole possession of 10th place on the NBA's all-time playoff scoring list with 3,899 points. Wade actually outscored the Sixers 15-13 in the second, with the 13 points scored the fewest for the 76ers in a quarter this season.
Dragic also shot 5 of 6 for 11 points in the first half.
--Field Level Media
Miami | Philadelphia | |
Dwyane Wade 28 | Scoring | Ben Simmons 24 |
Kelly Olynyk 6 | Assists | Ben Simmons 8 |
James Johnson 7 | Rebounds | Ersan Ilyasova 11 |
Dwyane Wade 6 | Free Throws Made | Marco Belinelli 4 |
James Johnson 3 | Steals | Dario Saric 4 |
Josh Richardson 3 | Blocks | Ben Simmons 2 |
Team | Points | FG% | 3PM-3PA | FTM-FTA | Assists | Rebounds | Blocks | Steals | Turnovers |
Miami | 113 | 48.8 | 9-25 | 24-30 | 23 | 46 | 7 | 8 | 15 |
Philadelphia | 103 | 41.7 | 7-36 | 16-22 | 22 | 49 | 5 | 7 | 15 |