The block bounced above a row of cameramen and into the seats in the second quarter of the Heat's 98-79 victory.
James dribbled just inside the 3-point line with about 8:25 remaining in the second frame. He drove in slowly against Heat forward Kelly Olynyk before picking up the ball and going toward the rim.
James ended up fading away to the left of the hoop, as Olynyk jumped to defend. Wade came in from behind and put his right palm on the ball, dislodging it from James' hands.
The Heat veteran stared at his hand in celebration.
James scored a team-high 18 points and had seven assists and six rebounds in the loss. He also committed six turnovers.
Wade netted 12 points and had four blocks, four assists and two rebounds in the victory. Olynyk led all scorers with 19 points. Wade had another block of James in the fourth quarter.
The loss ended Cleveland's five-game winning streak and prolonged the Cavaliers' 14-game losing streak in Miami.
James hasn't won in Miami -- as a member of the Cavaliers -- since 2010.