A 17-2 run in the third quarter helped the Quakers knock off the Dragons at The Palestra on Friday.
Penn fell behind by nine at the end of the first quarter and trailed by four before its furious third-quarter run.
With the victory, Penn improves to 8-1 on the season, which is its best start in program history.
Freshman guard Kayla Padilla scored 17 points and was a catalyst in the third quarter by knocking down two threes.
Tori Crawford, Phoebe Sterba and Eleah Parker, who also recorded five blocks, finished with 10 points apiece.
The Quakers will spend the New Year in Hawaii, playing the Rainbow Warriors on New Year’s Eve and Chaminade on Jan. 2.
Drexel falls to 6-5 and will host Maine on Dec. 30.
Freshman foward Claire Melia led the Hawks with 18 points in a victory over the Crimson in the FAU Holiday Classic in Boca Raton, Fla. on Friday afternoon.
Melia added six rebounds, three assists and two steals.
Sophomore guard Katie Jekot added 15 points for the Hawks.
St. Joseph’s defense was on full display, holding Harvard to 36.2 percent shooting and 13.6 percent from three-point range.
The Hawks improved to 5-5 and will face Furman in the championship game on Saturday at 4 p.m.