Hassan Whiteside added a double-double of 16 points and 11 rebounds, while Mario Chalmers contributed 16 points off the bench for Miami. The Heat used a 19-5 first half run to take an 18-point lead into the break, and led by as many as 25 in the second half.
Miami has now won both games against James in Miami this season, and 9 straight home games overall against Cleveland.
James finished with 26 points on the night, including 16 in the fourth quarter. He was playing in his 900th career regular-season game. Kyrie Irving added 21 points for the Cavs, who saw their 4-game win streak come to an end.
Wade out-performed LeBron on Christmas day, the last time LeBron visited Miami, when he scored 24 points in the first half alone. He scored 16 points in the second quarter alone on Monday night, which matched Cleveland's second quarter total.
The Cavaliers were playing without Kevin Love for the second straight game, who was sitting out for rest. He is expected to play in their next game on Wednesday.
Miami ran their record to 30-36 on the season, and will host the tough Portland Trail Blazers on Wednesday night. The Cleveland Cavaliers fell to 43-26 overall and will host the Brooklyn Nets on Wednesday.