Indiana (6-1) has won two straight and three of its last four in a showcase for two of college basketball's power conferences.
The difference was obvious: Indiana shot 53.2 percent from the field, compared with a season low 36.1 percent for Pittsburgh. Plus, Indiana had a 48-28 scoring edge in the paint.
The Hoosiers trailed only twice in the game, 2-0 and 4-2, and were in control most of the game.
After leading 45-37 at the half, Pitt closed to 47-41. But the Hoosiers went on a 16-4 run and pushed the lead to as much as 23.
It was Indiana's most impressive game of the season.
Offensively, the Hoosiers converted regularly when they got near the basket. Defensively, they forced the Panthers to settle for jumpers.
The combination was too much for Pittsburgh, which fell to 1-1 all-time in the challenge after joining the ACC last season.
Indiana started seizing control midway through the first half.
James Blackmon Jr. hit a 3-pointer to give the Hoosiers a 22-18 lead, spurring two quick Indiana flurries. After a Pittsburgh layup, Holt completed a three-point play, Max Hoetzel hit a 3 and Troy Williams scored on a short runner to extend the lead to 30-20.
Pittsburgh finally answered with Newkirk's 3, but the Hoosiers scored the next six to take a 36-23 lead.
The Panthers got as close as 42-37 when Cameron Johnson made a 3 in the final minute, but Holt completed another three-point play before halftime.