Penn overcame early foul trouble and opened up a 15-8 lead 6:17 into the first half.
The Big Red slowly found their range and took the lead for good on a lay-in by Geoff Reeves with just under seven minutes remaining in the opening half.
Cornell led 44-29 at halftime and was never seriously threatened by Penn in the second half.
Cornell has won 10 of its last 12, including nine straight before Friday's loss.
Sophomore guard Harrison Gaines led Penn with a career-high 20 points, including 17 in the second half.