Wade, returning from a sprained ankle, caught fire after the Heat had entered the fourth quarter tied with the Knicks at 71.
He finished 10-of-18 from the field with nine rebounds as Miami won in a potential preview of a first-round playoff series. It was only their second victory in 10 road games against opponents with winning records.
New York got 42 points from Carmelo Anthony but still lost for only the second time in six contests.
Celebrity Families of 2014 [PHOTOS]