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.
Former Titans kicker dies in car crash
UPI Sports Results for September 20, 2014