James, playing with a protective mask after missing Monday's victory over Chicago, netted 13-of-19 shots from the field, and Wade drained 10-of-13 as the Heat cruised to a sixth straight win.
Carmelo Anthony put in 29 points for the reeling Knicks, who fell for the seventh time in eight games.
Tyson Chandler added 19 with 16 rebounds.
2014: NFL Cheerleaders [PHOTOS]
Michael Sam cut from the Dallas Cowboys