Chris Bosh finished with 16 points and 14 rebounds for the Heat, who pulled away in the fourth quarter of a possible playoff preview. Miami is second in the Eastern Conference and New York came into the game tied for seventh, although they fell back behind Philadelphia after the loss.
Carmelo Anthony scored 42 points for the Knicks, but had only two baskets in the fourth quarter, perhaps tired after playing 43 minutes. New York had its nine-game home winning streak snapped.
Anthony had the Knicks hoping he could pull out another game against a power team after scoring a season-high 43 last Sunday in overtime against Chicago. His tip-in gave New York a two-point lead with 9 ½ minutes left, but by the time he had his other field goal on a 3-pointer with 1:28 remaining, Miami had opened an 11-point cushion.
JR Smith scored 16 points for the Knicks, who lost all three games against the Heat.
Wade moved easily and shot 10 of 18 after missing the last game to rest his ankle. Miami has won two in a row after back-to-back losses last week against Boston and Chicago.
Miami held a few nine-point leads in the third, but the Knicks cut it to three by period's end, then got a tying 3-pointer from Steve Novak to open the fourth and Landry Fields followed with a basket to put New York ahead in the opening minute.
It was close for the next six minutes before Wade and James hit jumpers after Joel Anthony tipped in a miss, a flurry of six straight points that gave Miami an 87-80 lead. The Knicks, relying on jumpers most of the game, simply couldn't hit any, and lacked much inside presence when Tyson Chandler appeared slowed by knee pain after landing awkwardly in the third quarter.
The Heat were scheduled to play their season opener here in the original 82-game schedule that was scrapped because of the lockout. They also would have opened here in a revised 72-game season that never developed when owners and players couldn't agree to a new deal in time.
Instead, they ended up being the last Eastern Conference team to visit Madison Square Garden, an arena that has undergone renovations since their last trip here.
They could become plenty familiar with the place in the coming weeks if the teams renew what was a fierce playoff rivalry in the late 1990s.
It had a playoff look Sunday, with orange shirts being worn by fans all around the court — though not by Jay-Z and Beyonce sitting courtside.
Only the Heat looked playoff ready at the start. The Knicks missed their first three free throws and Miami led by as much as 11 in the first quarter before settling for a 29-22 advantage that would have been much bigger if not for Anthony's 14 points.
Miami stalled in the second quarter, Wade slamming the ball to the floor in frustration after one basket as the Knicks rallied behind Anthony and their reserves to lead before three before the Heat took a 46-44 edge into halftime.
The Heat had a brief scare in the third when James went down after twisting his ankle when he backpedaled into some fans after hitting a corner jumper. He stayed down for a moment but remained in the game after a timeout.