The Orange received a strong effort from C.J. Fair and Tyler Ennis, who combined for 33 points and 15 rebounds in a losing effort.
The Flyers were led by Dyshawn Pierre and Jordan Sibert, who combined for 24 points in the victory.
Sophomore guard and Duke transfer Michael Gbinije came off the bench to pitch in 8 points for the Orange.
After starting the season on a 25-0 run and a No. 1 overall ranking in the nation, the Orange finished 28-6.
This is the first time this season SU lost to an opponent after holding them to under 60 points.
No. 11 seed Dayton (25-10) is having a Cinderella like tournament after upsetting No. 6 seed Ohio State 60-59 on Thursday and with the victory, advances to the Sweet 16 to play the winner of Stanford and Kansas.
This is Dayton's first Sweet 16 since 1984.