Will Sheehey scored 19 points to help No. 1 Indiana defeat Ball State 101-53 on Sunday.
Jordan Hulls scored 17 points, Cody Zeller scored 15 and Christian Watford had 11 points and 10 rebounds for the Hoosiers (6-0).
It was Indiana's largest victory margin in a 21-game series that began in 1934. The Hoosiers' previous largest victory margin against the Cardinals was 43 points in 1946 and 1983.
It was Indiana's first game since winning the Progressive Legends Classic with victories over Georgia and Georgetown in Brooklyn, N.Y.
The Hoosiers already had been averaging 86 points per game before shooting 61 percent from the field against the Cardinals.
Majok Majok scored 18 points and Jauwan Scaife added 11 for Ball State. The Cardinals (2-2) were coming off a 20-point loss to Indiana State.
The Cardinals were outrebounded 42-29 and shot just 31 percent from the field.
Sheehey, a junior forward, missed his career high by two points.
Indiana's Maurice Creek scored a season-best nine points in 14 minutes. He averaged 16.4 points as a freshman in 2009-10 before suffering a season-ending broken left kneecap. Thirteen months later, he was diagnosed with a stress fracture in his right kneecap, ending his season again. He missed last season with a ruptured Achilles' heel.
The Hoosiers improved to 20-1 all-time in the series, having only lost to the Cardinals in 1937.
The game was close early, but Indiana went on a run when Sheehey and Creek entered the game. A breakaway dunk by Zeller put the Hoosiers up 28-13.
The Hoosiers shot 64.7 percent in the first half to lead 50-19 at the break. Indiana missed four of its first six shots before making 20 of 28 the rest of the half.
The bench scored 20 points on 8-for-10 shooting before the break. Sheehey, a reserve, scored 11 points and Creek scored nine off the bench in the first half. Indiana held the Cardinals to 5-for-25 shooting and forced 10 turnovers before the break.
After establishing its inside game in the first half, Indiana went to the perimeter early in the second half. A 3-pointer and a free-throw-line jumper by Hulls bumped the lead to 64-23, and a three by Victor Oladipo pushed the lead to 44 with 14:35 to play.
A 3-point play by Austin Etherington in the final minute put the Hoosiers over the century mark, and the remaining fans gave the Hoosiers one of the loudest cheers of the night.