Skinner took exception to Guentzel hitting Buffalo goalie Craig Anderson's glove with his stick when the goalie had the puck covered.
"It wasn't much, but it was clear as day I was freezing it for three seconds ahead of time," Anderson said. "There's no reason to do that and then that threw us. And then he slashes 'Skinny.' Skinny slashes back, and before you know it, we're at the short end of the stick on that. That's just the way she goes."
Rakell had a goal and an assist, Evgeni Malkin had two assists, and Tristan Jarry made 28 saves for the Penguins (15-8-4), who won their fourth straight and are 9-1-1 in their past 11 games.
Casey Mittelstadt had three assists, and Anderson made 29 saves for the Sabres (12-13-2), who had won their previous two games.
"We've got to hold our composure and we've got to use that as a learning curve, learning tool for us," Anderson said. "It's one of those things where staying in the moment and getting the two points is more important than getting frustrated. That's what it was. It was just frustration on our part that we have to learn from."
Brock McGinn scored on a one-timer from the right face-off circle at 16:30 of the third period to give Pittsburgh a 3-2 lead.
Kyle Okposo tied it 3-3 at 18:30, scoring on a one-timer in the slot off a pass from Jack Quinn during a 6-on-4.
"We played a good hockey game tonight, and I thought that they were on their heels for most of the night and we had control of the play," Okposo said. "They made that push in the third, able to battle to back, tie the game, and just unfortunate result tonight."
Guentzel gave the Penguins a 1-0 lead with a power-play goal at 15:36 of the second period after Malkin's pass deflected off the stick of Sabres defenseman Mattias Samuelsson.