And he did so while honoring Joaquin Oliver, one of the 17 shooting victims who died Feb. 14 in Parkland, Florida.
Wade's jumper with 5.9 seconds remaining was the game winner.
Afterward, he reacted to how special the moment was.
"From the standpoint of away from the game of basketball, as I continue saying, just understanding how important we are as professionals," Wade said. "And for me, it's just giving whatever I can to people who believe in me, and especially people who were happy about me coming back here [after the trade from the Cleveland Cavaliers earlier this month] who embrace me the way that I only can dream of with me coming back home. So just paying some due respect to [Oliver] and his family tonight."
Wade later posted on social media about the night, singling out both his late agent, Henry Thomas, and Oliver.
Oliver was a student at Marjory Stoneman Douglas High School and also was a huge Heat fan. His parents revealed Sunday on the Univision talk show "Al Punto" that their son was buried in his Wade jersey, something not lost on the 12-time All-Star when asked about it Monday.
"You really can't put that in words. You hurt for the family," Wade told reporters. "If you ever get the opportunity to speak to them, you just try to hope the time where he was alive that you were able to bring some type of joy to his life and something memorable. A story that his family and you guys can talk about."
Wade crafted another story Tuesday with a performance that left teammates and foes in awe of the 36-year-old guard.
"There's something about Dwyane Wade when you put that Miami Heat jersey on and play in front of these fans,'' Heat coach Erik Spoelstra said. "He becomes somebody very special.''
Sixers guard JJ Redick, who missed a 3-point try at the buzzer that would have won it for Philly, offered his take: "D-Wade down the stretch was amazing."