James and Wade just overwhelmed the Warriors from the start.
Wade lobbed an alley-oop from half court that James finished with two hands early in the first quarter. James hit Wade slicing down the lane for a dunk moments later for his 5,000th career assist, and James made a 3-pointer after falling hard on his right elbow a play earlier to give the Heat a 23-14 lead.
James, who made 11 of 20 shots from the floor, needed 18 points entering the game to become the 38th NBA player to reach the milestone.
Previously, the youngest player to score 20,000 points was Lakers star Kobe Bryant, who got there when he was 29 years, 122 days old. James was 28 years, 17 days on Wednesday.
"He probably would've had it sooner if he didn't decide to come down here to South Beach," Wade said. "It's just a testament to him as a player."
Only Bryant, Wilt Chamberlain (29 years, 134 days) and Michael Jordan (29 years, 326 days) reached the latest milestone before turning 30.
James also is the 13th player with 20,000 points and 5,000 assists. The only active players to reach both marks are Bryant and Boston's Kevin Garnett.
With the long-awaited record out of the way, James and Wade switched roles and opened the second half almost the same way they began the first.
Wade tossed an alley-oop just inside half court to James while two Warriors defenders watched the three-time NBA MVP soar for the slam, part of a scintillating 26-6 surge filled with highlights to open the third quarter and put the Heat ahead 78-44.
In a 104-97 loss at Utah on Monday, Spoelstra sat Wade and played Chris Bosh for just 40 seconds in the fourth quarter in a decision that had been critiqued and questioned for the past two days by fans and national media. The Heat sliced a 19-point deficit to two without both before falling short.
This time, the Big Three watched the final 12 minutes smiling from the bench.
"Hopefully," Spoelstra said, "we can put to rest everything that happened the other night."
NOTES: In terms of games played, James is the seventh-fastest to join the 20,000 club. Wednesday was his 726th regular-season game. Chamberlain needed only 499 games to score 20,000 points. ... The Warriors are 13-3 against the Eastern Conference this season. The two other losses came against Orlando. ... Heat backup F Shane Battier returned after missing two games with a hamstring injury. He had two rebounds and finished 0 for 3 from 3-point range in 10 minutes.