The Heat led throughout but needed to survive a late Nuggets rally to claim a first victory in Denver since January 2002.
Despite trailing by as many as 19 points on the night, the Nuggets (4-5) were just one behind with 65 seconds remaining but Danilo Gallinari's wide-open three-point shot fell woefully short.
Norris Cole then stuck a dagger in the home fans heart by nailing a triple of his own just 14 seconds later after three-time league MVP and eight-times All-Star Lebron James trusted him with the shot and fed him the ball.
"We just have high self esteem and we have confidence in everybody's ability that is on the floor," James, who usually loves making the clutch plays down the stretch, said of the play.
"I was happy to see him knock it down. They made their run, they're a great team at home but we were able to withstand them," James said.
Wade sat out the contest at the Pepsi Center in Denver after spraining his left foot earlier this week against the Los Angeles Clippers but the Heat overcame his absence to move to 7-3.
James took charge for the Heat, leading the team with 27 points, seven rebounds and 12 assists and he was helped by Shane Battier (18 points), Chris Bosh (14) and Mike Miller (12) in what was an impressive team performance.
The Heat were on fire from distance, claiming 39 points at 48 percent from outside the three-point arc compared to the Nuggets 18 points at 30 percent.
But James preferred to talk up a better defensive performance by Miami, who have regularly allowed over 100 points this season.
"In order for us to win throughout the course of the season we have to defend," James said.
"We've had some slippage early in the season but the first thing about it is we own it and we know it.
"It's not just coming from the coaching staff. We know our staple is defence, we know it's going to give us the best opportunity to win, to defend and rebound and I was glad to see we got back to that tonight."
It wasn't all great news for the Heat with Mario Chalmers playing just seven minutes for Miami before succumbing to injury.