All-Big Ten point guard Tim Frazier had a career-high 13 assists along with 11 points for the Nittany Lions (8-3), who won despite having only 10 free-throw attempts as compared to the Dukes' 34.
Ovie Soko had 19 points to lead the Dukes (3-4), who shot 27 percent from the field and made just four of 23 attempts from 3-point range.
Soko, who made 12 of 14 free throws, played just 22 minutes before fouling out.
Duquesne has lost four of its past six and fell to the Nittany Lions for the second consecutive season.
Penn State's Donovon Jack had nine points, 12 rebounds and six blocks.
Playing its second game in the city of Pittsburgh over a nine-day span, Penn State fared better than it did in a nine-point loss at Pitt on Dec. 3. Counting a 90-77 win over Marshall in between, the Lions have combined to hold their past three opponents to 27.8 percent first-half field goal shooting.
Unlike they did against Pitt (which shot 58.5 percent in the second half), however, Penn State continued to stifle the Dukes through the final buzzer. Other than a stretch of about seven minutes midway through the second half, Duquesne's shooting was cold from all over the court.
Penn State began the second half on an 8-2 run to open up a 15-point lead. The Dukes answered by scoring 14 of the next 18 points of the game to pull within five -- but that would be the closest the Dukes would get.
Minutes later, Duquesne was within 50-44 after a pair of free throws by Soko with 8:40 left. But the Lions answered with an 8-0 run that all but put the game away. Penn State led by as many as 19 in the second half.
Duquesne shot 25 percent from the field -- including two of 12 from 3-point range -- in the first half. The Dukes also missed seven of 17 free throw attempts.
Jack, a former verbal commitment to Duquesne who switched to Penn State after the Dukes fired former coach Ron Everhart, had a career-high 11 rebounds. He has combined for 13 blocks over the past two games.
Through the first 37 minutes of the game, Penn State went to the foul line just six times.