The 37-year-old hit a three-pointer on the buzzer as his team trailed Golden State Warriors 125-123.
In the dying moments of the NBA clash at Miami’s American Airlines Arena, Wade was cut off after bringing the ball up the floor and passed back out to Dion Waiters.
But with no clean look, Waiters passed back to Wade with just three seconds remaining.
Wade faked to shoot once before his second attempt was almost tipped out of his hands.
But he hung on and shot again, with a seemingly impossible shot while off-balance on just one leg.
“Wade has had a lot of game winners but this might be the craziest one.”
Kazeem Famuyide, journalist
He sank the three, giving Miami a 126-125 win over the in-form Warriors.
As he wheeled away in celebration, fans went wild, and many took to social media in disbelief at what they’d seen.
One fan tweeted: “D Wade game-winner. Best moment of the season.”
NFL star Le’Veon Bell also tweeted simply: “D Wade!!!”
Journalist Kazeem Famuyide wrote: “D Wade has had a lot of game winners but this might be the craziest one.”
While another fan added: “D Wade forever.”
Byron Saenz said: “D Wade at home in his final season against Golden State, another classic game-winner. Can’t make this up.”
Wade was drafted by the Heat in 2003, leading them to their first-ever NBA Championship, followed by back-to-back wins with LeBron James in 2012 and 2013.
This season, Wade rejoined Miami after a two-year spell away at Cleveland Cavaliers and first Chicago Bulls.
He is Miami’s all-time leader in points, games, assists and steals, as well as shots made and taken.
Incredibly for such a successful player, the shot was Wade’s first game-winning buzzer beater while his team were losing in his entire career, having missed the previous 14.
Miami are now two places outside of the Eastern Conference playoffs.