Dwyane Wade had 33 points, Mario Chalmers scored 14 and Chris Bosh added 13 to help the defending NBA champions improve to 39-14. The Heat have a comfortable 5½-game lead over Indiana in the Eastern Conference.
They've won four in a row on the road, including impressive wins over Oklahoma City before the All-Star break and Chicago on Thursday.
Jrue Holiday scored 21 points and Nick Young had 19 for Philadelphia, which continues to fall further behind in the playoff chase. The Sixers entered 3½ games behind Milwaukee for the No. 8 spot in the East.
A rare sellout crowd turned out for the nightcap of an NHL/NBA doubleheader at the Wells Fargo Center to see James, Wade and Co. There were even scalpers outside the arena selling tickets before the game for one of the few big draws of the season.
Fans roared when Spencer Hawes rejected James' shot late in the first quarter, swatting the ball back at the three-time NBA MVP's face.
Many of the same people jumped to their feet and cheered when James threw down a thunderous dunk off an alley-oop pass from Norris Cole late in the third quarter. By that time, the Heat were up 85-63 and the crowd was more interested in seeing James make a highlight play than rooting for the Sixers.
James got his first "Ooohs" and "Ahhhs" after a no-look backdoor pass to Bosh for an easy layup in the first. Chalmers followed with a rainbow 3-pointer and a reverse lay-up to give the Heat a 24-22 lead and they never trailed again.
James collected his 10th rebound early in the fourth quarter to get his seventh triple-double since joining the Heat. He got a mixture of cheers and boos when he went to the bench shortly afterward.
Wade came in after a brief rest and continued his hot shooting, scoring six straight points on a driving layup, two free throws and a long jumper. He was 12 of 14 at that point before missing a 3-pointer.
While the Heat are gearing up to make a run at a repeat, the Sixers have lost four straight to fall a season-worst nine games below .500 at 22-31.
It's been a disappointing year for Philadelphia, which knocked off top-seeded Chicago in the first round of the playoffs a year ago and then took Boston to seven games in the conference quarterfinals.
A season that began with promise after the acquisition of center Andrew Bynum quickly fell apart. Bynum has yet to play a game this season because of bone bruises in both knees. He said earlier in the week he plans to play at some point. At this rate, it won't matter much for the Sixers.
Notes: The Flyers beat the Winnipeg Jets 5-3 in an afternoon hockey game. ... The Heat have won 12 straight regular-season games against Philadelphia. The Sixers won one playoff game against Miami in the first round of the 2011 playoffs. ... Heat G Mike Miller remained in Miami because of ear problems resulting from a head cold. He's missed three straight games. ... James has scored in double figures in 472 straight games, sixth-best in NBA history.