Philadelphia lost its shooting hand in the fourth quarter and Cleveland took the lead for good midway through the final period.
Zydrunas Ilgauskas hit a jumper that broke an 85-85 tie and gave Cleveland a lead it did not relinquish the rest of the way. A pair of buckets by Jamario Moon and a layup by James put Cleveland ahead 93-85 with just under 4 minutes to play.
Ilgauskas finished the night with 13 points. Mo Williams added 18 points and eight rebounds.
The Sixers, who shot 4-for-23 in the final 12 minutes, were led by Lou Williams' 22 points. Thaddeus Young scored 21 and Eldon Brand added 18.