With Wade sidelined due to an ailing knee, James took on the burden of leading the scoring and pulling his team to within 2 1/2 games of the East-leading Chicago Bulls.
"It's never really mattered to me about scoring," James said after making 15-of-25 shots from the field. "I'm happy to get a good team effort against a playoff team."
The 76ers' defeat dropped them 1 1/2 games behind Boston in the Atlantic Division as they sit seventh in the overall East standings.
In the final month of a truncated regular season, shortened from 82 to 66 games due to a protracted labour dispute, the fight for playoff places continues to gather steam throughout the league.
Well behind Miami, and third in the conference, the Indiana Pacers strengthened their position with a 112-104 comeback win against the New York Knicks.
The Pacers blasted the Knicks 40-17 in the fourth quarter to complete the dramatic turnaround. Despite the loss, New York have a 1 1/2-game advantage in the battle for eighth spot.
Fifth-place Orlando are now just one game up on Atlanta following their 102-95 defeat at the hands of Detroit.
Over in the Western Conference, San Antonio crushed Cleveland 125-90 to pull within two games of top seed Oklahoma City.
The Spurs raced to their eighth straight victory to heap pressure on the Thunder.
Meanwhile, Memphis overcame Golden State 98-94 to earn their third consecutive triumph. The Grizzlies are fifth in the West and trail the Los Angeles Clippers by one and a half games.
The Los Angeles Lakers enjoyed a 91-87 victory over New Jersey that gave them a 1 1/2-game lead over the Clippers in the race for third-place in the West heading into Wednesday's showdown with their city rivals.