Even with all of the starters sitting out the fourth, the 130 points was the most ever scored by the Cavaliers in a playoff game.
Kyrie Irving had 23 points for the Cavaliers, who return home with a chance to finish off the Celtics in Cleveland. It would be the third straight sweep this postseason for the defending NBA champions, who also won the last three games of last year's finals.
Game 3 is Sunday night.
"It's one game. I don't care if you win by 200 points," Cavaliers coach Tyronn Lue said. "We're going back home, we're not going to get comfortable. We understand that this is a good team. They're not No. 1 in the East for no reason."
The Celtics played the second half without Isaiah Thomas, who had a strained right hip. Celtics coach Brad Stevens said the star point guard had a nagging injury that he aggravated a week ago during the second-round series against Washington.
Asked how much that hurt his team, Stevens said, "Not 44 points worth."
"I don't want to put that on any one guy," he said. "Ultimately, they were terrific. We were poor. You've got to be able to pick up the slack, certainly, when other guys aren't available."
With both teams going to their benches in the fourth, the only suspense was whether the Celtics could avoid the worst playoff loss in franchise history. The Orlando Magic beat them by 47 points in the first round of the 1995 postseason.
Still, it was the worst home playoff loss ever for the most-decorated franchise in NBA history.
"It is embarrassing," guard Avery Bradley said. "As a man, as a basketball team, it will say a lot about us how we respond."
Thomas finished with just a pair of free throws, missing all six shots from the field. Rookie Jaylen Brown scored a career playoff-high 19 points for Boston.
The game tipped off about 15 minutes after the NBA announced that James Harden, Russell Westbrook and Kawhi Leonard were the finalists for the MVP award — the first time since 2008 that James won't finish in the top three.
Lue chuckled when he found out after the game that James was not a finalist.
"You've got to give the award to different people every now and then," Lue said. "But to me, LeBron's the MVP."