James donned a dark mask to protect his broken nose and was clearly unencumbered, hitting 13 of 19 shots and topping 30 points for the fifth consecutive game.
Wade shot 10 for 13 from the field for Miami, which outscored New York 23-3 over the final 7:02 of the third and won its sixth straight.
The Heat shot 61 percent, while the Knicks shot 37 percent.
Carmelo Anthony scored 29 points for New York, but none in the final 21:38. Tyson Chandler had 19 points and 16 rebounds, and J.R. Smith added 11 points for the Knicks, who fell to 2-10 in February.
Norris Cole, Mario Chalmers and Ray Allen each scored 11 points for the Heat, who are 41-7 in February games over the last four seasons.
The blowout was so pronounced that TNT cut away from the game midway through the fourth quarter, opting instead to show part of the third overtime of the Washington-Toronto game. By then, all the stars in Miami were on the bench anyway.
When that game ended, TNT came back for the end of Heat-Knicks, missing about 4 minutes of game action.
James got the buzz for this one going just before tip-off, strapping the mask over the top half of his face, the deviation from the usual clear-plastic look enough send Twitter users into some sort of commenting overdrive.
More importantly to the Heat, the mask didn't seem to impair his vision. James had 11 in the opening quarter, the Heat finished the period with a six-point lead and soon stretched the margin to 16 in the second quarter. A hook shot from Wade in the lane was his seventh straight make, giving Miami a 43-27 lead and indicating things would be a runaway.
Eventually, they indeed would.
But New York made it interesting for a bit.
Anthony said a few hours before the game that every outcome is critical to the Knicks now, especially with playoff chances dwindling. And he backed up those words with a brilliant flurry, scoring all 16 of his second-quarter points in the final 5:52 of the period as New York erased just about every bit of that big Miami lead.
With 8:36 left in the third, Anthony set up J.R. Smith for a jumper that got New York within 64-61.
And from there, it was all Miami.
That's when the huge run to end the third got started. The Knicks missed 12 of their final 13 shots to end the third — their only field goal in the final 8½ minutes was a layup by Tim Hardaway Jr. — and the Heat just got rolling. For some perspective, James had 12 points in the quarter while the Knicks, total, had 14.
Shane Battier set up James for a down-the-lane dunk that got Miami's lead back to double digits at 72-61 and the snowball just kept growing. A 10-0 run in the final 2:21 of the quarter turned it into a runaway; James got fouled by Anthony and turned it into a three-point play with 1:58 left, then beat Anthony on a cut and accepted a pass from Cole for an easy layup on the next possession.
One trip later, Allen hit a 3-pointer, and just like that, Miami's lead was 23, the outcome quickly becoming academic.
NOTES: It was the first time in Miami as an opponent for Hardaway Jr., with the Knicks bench at the end of the court where Tim Hardaway Sr.'s retired jersey number hangs from the rafters. ... Wade missed about three minutes in the first quarter to get an ankle re-taped. ... Dwayne "The Rock" Johnson was among the stars in attendance. ... The Heat didn't get a single offensive rebound until the fourth quarter.