All 11 players for Duke who played scored on the night with no Duke student-athletes playing over 25 minutes in the game.
Abby Waner scored 15 points, had six assists and six steals in her collegiate debut, after coming off a senior year in high school where she was named National Player of the Year.
Duke improves to 4-0 in the all-time series with Penn State.
Alison Bales finished with a team-best 15 points, nine rebounds, three blocks and hit 5-of-7 field goals.
With the victory, the Blue Devils broke Penn State's 20-game home winning streak.
Senior Monique Currie had 12 points while also totaling two rebounds in 22 minutes.
Duke moves to 23-8 in season openers, while the Blue Devils are 12-2 in the Coach G era.
In the first half, Duke was called for 15 fouls, while PSU had 10.
As a team, the Blue Devils dished out 25 assists and shot 70.4 percent in the second half.
Duke shot 57.4 percent from the field on the night.
Abby Waner became the eighth freshman to start her first collegiate game at Duke under Head Coach Gail Goestenkors. Overall, she is the 17th player to start her first game as a freshman for the Blue Devils.
Sophomore Wanisha Smith tied a career-best with five steals.
After totaling a NCAA-record 267 blocked shots last season, Duke finished with seven on the night.
Duke will continue its two-game road trip with a 2 p.m. contest on Sunday at Old Dominion.