James took a moment early on to ask a heckler to lay off his family, then helped Miami pull away for its eighth straight victory. A fan who said he was seated near the heckler said James was being taunted when he told the fan he could say whatever he wanted about James, but: "Don't say anything about my family - be respectful or we're going to have a problem."
James finished with eight rebounds, narrowly missing a triple-double.
Miami entered the night tied atop the conference with Boston, which was off after losing to the Los Angeles Lakers on Thursday.
The Celtics host the Heat (39-14) on Sunday.
Wade threw down an impressive alley-oop dunk from James in the first quarter to give his team a 16-7 lead. Although the Pistons trailed by only four after that quarter, Miami broke the game open with a 12-2 run to start the second.
Austin Daye scored 18 points for Detroit.
Chris Bosh had 17 points and 10 rebounds for Miami, which had six players in double figures, including all five starters. Reserves Mike Miller and Eddie House made 3-pointers during the run to start the second quarter, which Wade capped with a bank shot for a 37-23 lead.
Miami later went on a 21-5 run to make it 64-41. The Heat led 64-43 at halftime and weren't seriously threatened after that.
The game might have been more interesting for what was taking place off the court. While James was dealing with a heckler on one side of the court, a more famous fan was taking in the action on the other. Aretha Franklin was on hand for the game in what was believed to be one of her first public appearances since undergoing surgery Dec. 2 for an undisclosed ailment.
Also before the game, representatives for Pistons owner Karen Davidson and investor Tom Gores acknowledged that Gores is negotiating to try to buy the team.
If he does take control, he'll have a challenge on his hand rebuilding the Pistons, who never led against Miami. The Heat aren't known for their depth, but their starting five outscored Detroit's 77-41.
Mario Chalmers and Zydrunas Ilgauskas scored 10 points each for Miami, and Miller finished with 16.
Ben Gordon scored 16 points for the Pistons, and Tayshaun Prince - the only Detroit starter in double figures - added 11.
NOTES: Detroit Lions DT Ndamukong Suh was also at the game. ... G Rodney Stuckey started for Detroit for the first time in eight games. He has been bothered by a right shoulder injury. ... Detroit's Richard Hamilton sat out with a sore right groin.