Kris Letang, who returned to the lineup 12 days after having a stroke, led Pittsburgh with 22:14 of ice time.
"It was great," Letang said. "I was getting anxious to get back out there. With the schedule, we don't have the chance to practice that much. Tried to prepare the best I could."
Jake Guentzel had two assists and Casey DeSmith made 37 saves in his first start since Nov. 26 for the Penguins (16-8-4), who are 10-1-1 in their past 12 games.
Ukko-Pekka Luukkonen made 28 saves, and Peyton Krebs scored for the Sabres (12-14-2), who lost 4-3 in overtime to Pittsburgh on Friday in the first of the home-and-home.
"This game, for sure, we gave up four minutes on the power play, or two power plays, to them early. Had to kill two penalties," Buffalo coach Don Granato said. "That got the crowd in it, it got them energized. ... We could have got more traffic and we could have had a greater shot mentality."