James was in the starting lineup after missing the previous two with an injured right ankle, and the league's leading scorer recorded his 26th double-double. He entered the game averaging 30.0 points, 8.5 assists and 7.2 rebounds.
Mo Williams added 21 points, Delonte West contributed 17 and Anderson Varejao had 12 points and 12 rebounds for the Cavaliers (51-15), who own the league's best record. Cleveland also won for the seventh straight time at the Wachovia Center.
Cleveland's bench outscored the Sixers' 44-20. Cleveland played without forward Antawn Jamison, who didn't make the trip because of left knee stiffness.
Andre Iguodala led the Sixers (23-42) with 30 points, Elton Brand added 24 and Thaddeus Young had 15. Samuel Dalembert grabbed 12 rebounds for Philadelphia, which dropped its third in a row and fell to 10-21 at home.
Trailing 98-95, the Sixers had a chance to get closer, but rookie point guard Jrue Holiday committed a turnover and West followed with two free throws.
The Sixers led 85-80 with 9:52 remaining, but Cleveland responded with an 8-0 run to go ahead 88-85. Jamario Moon scored five points during the spurt.
Thanks to some suffocating defense, the Cavaliers had plenty of chances. Williams hit a 3-pointer with 4:05 left to give them a 94-88 lead.
West scored 15 points and Varejao added 10, and Cleveland shot 57 percent in the first half on its way to a 61-57 lead. The Sixers kept it close thanks to 16 points apiece from Iguodala and Brand.
NOTES: Former Sixers coach Larry Brown denied a published report that he advised Comcast-Spectacor Chairman Ed Snider not to fire coach Eddie Jordan before the season ends. "No, I've had no direct conversations," Brown said. "I think I said it when I was in Philly. I don't think I said it the way you presented it, but I talked about what I thought about the coach, what I thought about the franchise and what I thought about their roster. I tried to be positive, because there's not a lot of positive stuff in the press about Philly." ... Sixers F Marreese Speights missed the game with a sprained right knee. ... Philadelphia Eagles running back LeSean McCoy attended the game.