Victor Oladipo set a career-high with 23 61 win at Mackey Arena on Saturday.
"This win is huge," Oladipo said. "We learned tonight to make better decisions and be poised when the game is on the line."
The Hoosiers got impressive efforts from freshmen Cody Zeller, 16 points and eight rebounds, and Remy Abell, who had a career-high 13 points as Indiana (18-6, 6-6 Big Ten) bounced back from a 68-56 loss at Michigan on Wednesday.
Robbie Hummel led the way for the Purdue (15-8, 5-5) offense with 16 points and 10 rebounds and D.J. Byrd added 15 points for the Boilermakers, who have now lost three of their last four.
Purdue had a chance to pull within two with two minutes to play but Will Sheehey pinned Lewis Jackson's layup attempt off the backboard and Christian Watford knocked down two at the line to put Indiana up 67-61.
Abell's trey on the next possession put the Hoosiers up 70-61 and sealed the victory for the road team, which closed the game on a 13-0 run.
"It looked like it meant more for them right from the start," said Purdue head coach Matt Painter. "If we could have made that play at the end when we were down four, and they ended up losing, it would have been a shame because they deserved to win the game. They were tougher than us, they were quicker to the basketball."
Oladipo scored seven points in a 13-0 run by the Hoosiers early on as they took the lead, 19-13, with 7:09 remaining in the first.
The Boilermakers shot a dreadful 8-for-40 from the field including 0-for-11 from three-point range as they entered the locker room facing a 33-22 deficit.
Purdue found its shot at halftime, however, as it came out of the intermission hitting 3-of-4 from long range to pull within seven, 43-36, with 15:52 left in the game.
This game marked the 197th meeting between these two teams...Indiana defeated Purdue for the first time since March 1, 2006...Purdue will look to bounce back at No. 3 Ohio State on Tuesday, while the Hoosiers host Illinois on Thursday...Purdue's Jackson had four assists to record his 400th career assist.