The Nittany Lions' (4-3) prevailed, 58-47. They capitalized on Penn's (2-6) Achilles' heel: poor three-point shooting.
The Quakers shot 22 percent (5 of 23) from beyond the arc, including 15 percent (2 of 13) in the second half.
Penn has lost seven of its last eight games against the Lions, dating back to 1995.
Penn freshman Tony Hicks scored 10 points, the only Quaker in double-digit scoring figures.
"That Penn team plays really hard," said Penn State coach Patrick Chambers, a Philadelphia native. "You know from the beginning what they're going to bring."
Penn pressed to begin the game, which didn't work out quite as planned as Penn State hit 5 of 7 three-pointers in the first half.
"Everybody needs to bring it," said Penn State guard Jermaine Marshall, who had a team-high 18 points. "Not just D.J. [Newbill], who brings it every game."
Newbill, from Strawberry Mansion High School, finished with 13 points, five rebounds, five assists, four steals - and only one turnover.
Penn's struggles were personified when, with 1:44 remaining, freshman guard Jamal Lewis was ejected for a flagrant foul on a Penn State fast break.
"You have a certain standard in the brand of basketball that we represent," Penn coach Jerome Allen said.
Penn entered Saturday one game shy of becoming the 10th Division I program to reach 1,700 wins. The Quakers will have to wait a little longer.