It was James' fifth straight game with at least 30 points, a franchise record. He's shot better than 60 percent in all five of those games.
Kobe Bryant had 28 points and nine assists for the Lakers, who also got 18 points from Earl Clark. The Lakers had eight turnovers in the fourth quarter, while Miami had none.
Wade also shot 12 for 18 for Miami, which shot 55 percent as a team and held a 38-29 edge in rebounding. James scored 20 in the second half and Wade had 18 in the final two quarters, but it took the reigning NBA champions until the final minutes before they could pull away.
Wade had five straight points for Miami, the last of them coming with 7:15 left when his three-point play put the Heat up 89-82 - at that point, their biggest lead of the day.
A minute later, Wade started what might have been Miami's signature sequence of the game.
He stepped in front of a pass by Bryant under the basket, then flipped it to Bosh before falling out of bounds. Bosh got the ball to Norris Cole, who beat Nash down the court, then lobbed a pass over his head to James, who soared for a slam that gave the Heat a seven-point lead once again.
With 3:25 left, James turned in another highlight.
He stole a pass, drove down the court and Nash - who found himself in the lane against a fast-charging James plenty of times Sunday, all to no avail - simply had no chance.
It was almost as if Nash wasn't even in James' field of vision. He leaped for a dunk, giving him 30 points and the franchise record, and Miami's lead was nine. Bryant scored on the next Lakers possession, but Shane Battier hit a 3-pointer with 2:42 left to put Miami up 100-90 for the first double-digit lead for either team all day.
And the Heat weren't challenged again.
The Lakers outscored Miami by one in the first quarter, and the Heat returned the favor in the second quarter. Los Angeles led by as much as seven in the half, the last time when Bryant made a fadeaway for a 44-37 advantage.
Miami came right back with a 7-0 run, James setting up Battier's 3-pointer to cap that little burst. And after James went to the bench with three fouls - the first time this season that's happened in a first half - the Heat didn't let the Lakers take advantage, and the clubs went into intermission tied at 53.
Much like the first half, the third period didn't allow either team much in the way of breathing room either, until the final seconds.
That's when James started flexing some muscle.
James scored Miami's last 11 points of the third, all in the final 4:20, and four of those came in the last six seconds. He was fouled by Clark and made the first free throw. Then the second attempt was tipped back out by Battier to James, who was just beyond the 3-point line. He connected from there, and the Heat took a 78-73 lead into the fourth.
NOTES: The Heat have now won six of their last seven games against the Lakers. ... James made his first five shots, which left him at 42 for his last 52 attempts from the floor to that point, a ridiculous 81-percent clip. ... Bryant had five assists in the first quarter, tying a season best. ... Celebrities in attendance included Miami Hurricanes coach Jim Larranaga, pro golfer Justin Rose and Donald Trump. Rapper Lil Wayne - a semi-regular in the crowd at Heat games - was there for the first half, then tweeted that he was ejected for rooting for the Lakers. ... LSU football coach Les Miles live-tweeted the game, noting that James is ''more athletic in person.''