The loss marks the first time Purdue has dropped four straight since Matt Painter's rookie season as head coach, where the Boilermakers finished 9-19.
Penn State was led by D.J. Newbill's 19 points and Tim Frazier's 18. Brandon Taylor also added 15.
Purdue trailed 51-49 just past the midway points of the second half, but Penn State pulled away with steady, consistent possessions. The Boilermakers pulled within five points in the final minutes, but the Nittany Lions responded again.
Looking to snap its skid, Purdue returns to action on Wednesday when it hosts Minnesota.