Charlotte lost its 16th straight game despite putting on a fourth-quarter surge. The Bobcats last won on Nov. 24.
James scored 27 points to go with 12 rebounds, eight assists and four steals. Miami won its sixth in a row and avoided a letdown after defeating Oklahoma City on Christmas Day in a rematch of last year's NBA Finals.
Charlotte trailed by 17 at halftime, but rallied within two when Gerald Henderson hit a 3-pointer with 7:16 left in the game. Miami then went on a 10-3 surge to regain control.
Dwyane Wade scored 13 of his 29 points in the fourth period and added nine rebounds for the Heat, winners of each of their last nine matchups with Charlotte.
Kemba Walker paced the Bobcats with 27 points.
James, who was called for his first foul since Dec. 8 during the Christmas Day meeting with Oklahoma City, picked up another one Wednesday.