James kept the Cavaliers in it for three quarters on a night they lost Shaquille O'Neal to a first-half thumb injury, then Mo Williams made four 3-pointers when Cleveland blew by the Celtics in the fourth, outscoring them 35-14.
Unable to stop Rajon Rondo or the Celtics in the first quarter, the Cavaliers turned up the defense in the fourth, limiting the Celtics to three baskets.
Ray Allen scored 21 points for the Celtics, who badly missed injured All-Star Paul Pierce (right thumb) when their offense went stagnant in the final 1-1/2 quarters.
Cleveland improved to 20-10 on the road, tying Boston for the best in the NBA, and avenged a home loss on opening night.
The Cavaliers opened a 5-1/2game lead over Orlando in the East while dropping Boston 7-1/2 games back in a tie for third with Atlanta.
In Oakland, California, Denver overcame Golden State in the Nuggets first game without coach George Karl since he revealed he has throat cancer.
Chauncey Billups had 37 points and nine rebounds and Carmelo Anthony added 27 points for Denver, which moved clear top of the Northwest Division, breaking a tie with Utah.
Karl stayed in Denver to receive treatment but is expected back Friday night at home against Detroit. Assistant Adrian Dantley directed the team against the Warriors.
The Nuggets set a season high with 16 3-pointers.
Stephen Curry had 30 points and 13 assists for Golden State, which twice whittled big deficits down to single digits, only for Denver to reply each time.
In Indianapolis, Milwaukee extended its winning streak to five games, edging Indiana.
John Salmons scored 20 points, and Brandon Jennings had 18 points and seven assists for the Bucks, who are 3-0 against the Pacers this season and now only one game off second place in the Central Division.
Danny Granger had 21 points for Indiana, which has dropped seven of eight.
Milwaukee had a 16-point lead in the third quarter, but that was cut to six with 4 minutes left in the game and then to just two with 31 seconds on the clock.
Granger converted two free throws with 10 seconds left, and Milwaukee hung on.
