After a slow start, Anthony exploded in the second half as the Knicks overturned a two-point deficit with a devastating second half burst at a packed Madison Square Garden.
"In that last minute or two minutes in the third quarter we got a little spurt before we started the fourth quarter," said Knicks head coach Mike Woodson.
"Fourth quarter, defensively, we picked up. We kept getting stop after stop and our offense got into a flow, like old times. It was nice to see."
Anthony, who won this season's NBA scoring title, also had nine rebounds and scored half of his 32 points during a 36-4 New York blitz. In the fourth quarter alone, the Knicks outscored the Pacers 33-13.
"I think he (Anthony) is great," Pacers head coach Frank Vogel said.
"He is a best of an offensive player and a competitor on the defensive end. He made a lot of tough shots and guarded pretty well tonight."
Iman Shumpert contributed 15 points for the Knicks, seeded second in the Eastern Conference playoffs, while Raymond Felton chipped in with 14 for the home team, including both three-pointers he attempted.
"I thought it was a total team hustle game," said Woodson. "Everyone was involved with deflections. Our hands were active and our rotations were right where they needed to be."
The Pacers, who had won Sunday's opening game by 102-95, got off to a slow start in Game Two, trailling by 13 points during the second quarter.
They briefly grabbed the lead in the third quarter but were unable to keep up with the Knicks when it mattered.
Paul George led the way with 20 points while David West had 13 and six rebounds. Despite the loss, the Pacers were upbeat about their prospects with games Three and Four being held in Indiana.
The eventual winner will advance to the Eastern Conference Final, against either Miami Heat or the Chicago Bulls.
"We didn't finish the third quarter well and it gave them some momentum heading into the fourth quarter," said George.
"And that's when Melo (Anthony) got off. We were scrambling and chasing them around throughout the whole quarter."