Cleveland entered Wednesday's contest in a 0-1 hole in the Eastern Conference playoff series. They left Quicken Loans Arena in Cleveland, Ohio, with the first-round series now tied.
James suffered his first loss in the first round since 2012 in the Cavaliers' 98-80 setback to the Pacers on Sunday. He scored 24 points and had 12 assists and 10 rebounds in that loss.
He started Wednesday's game by scoring the first 13 points of the contest, before the Pacers could make one field goal. James made a 3-pointer after a Pacers free throw, to complete his 16-point run for the Cavaliers.
Kevin Love was the only other Cavaliers player to even attempt a shot in the first four minutes of the game. He made a 3-pointer 5:25 seconds into the contest, becoming the first Cavaliers player other than James to make a basket.
James' stifling start included pull-up jump shots, reverse layups, turnaround fadeaways and finger rolls.
He finished the game with 46 points, 12 rebounds, five assists and two steals.
"It was just a feel," James told reporters. "Coach Lue called up the first play for me, and it went down. So we went back to it. I was able to hit another one and it just felt like I was in a really good rhythm. So I just tried to see how long I could stay in that zone and just try to make a mark on the game early on, especially after the way we started Game 1."
Victor Oladipo scored 22 points and had six assists for the Pacers. The Cavaliers and Pacers meet up again at 7 p.m. Friday at Bankers Life Fieldhouse in Indianapolis, Ind., for Game 3 of the series.