With the victory the Cavaliers took a 2-1 lead in the best-of-seven Eastern Conference semi-final series, which continues in boston on Sunday.
James, who earned NBA Most Valuable Player honors for the second season in a row, showed no ill-effects from an ailing elbow that has sparked widespread discussion.
"King" James finished with eight rebounds and seven assists, and his 21 first-quarter points was a Cavaliers playoff record for points in a period.
Antawn Jamison had 20 points and 12 rebounds, and Shaquille O'Neal added 12 points and nine rebounds for the Cavs.
Rajon Rondo, who had 19 assists in Boston's game two victory in Cleveland on Monday, had 18 points and eight assists.
Boston missed 10 of their first 13 shots, hitting just 27 percent in the first quarter as the Cavs built a 21-point lead.
The Celtics never recovered as the Cavs shot 59 percent from the field for the contest.
James wore a black compression sleeve on his right elbow, which became a hot topic after he shot a free throw left-handed in the closing minutes a first-round playoff game against Chicago.
"I know I'm going to hear a lot about the elbow, but I'm here to play basketball and give our team a chance to win," said the Cavs star, who has said he has battled a feeling of numbness or tingling in the arm. He has been diagnosed with a strained elbow and bone bruise.
He looked fine on Friday, as he made eight of 10 shots from the field in the first quarter.
Boston had stolen home court advantage from the Cavs with their game two triumph in Cleveland, but the Cavs were determined to regain the home advantage.
"We knew how important it was to come out and play aggressive after giving away game two," said James, who has now scored 2,000 playoff points in his career.
James scored eight straight points to make it a 10-point lead midway through the first, and seven points in an 11-0 scoring run that made it 36-15 with 19 seconds remaining in the period.
The Cavs led by 24 points in the second quarter and by 30 in the third. The Celtics didn't get within 20 in the whole second half.
Boston coach Doc Rivers pulled most of his starters with 6:37 remaining and James came out of the game with 5:41 to play - giving him a few more precious minutes to rest up for the remainder of the series.
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