Malkin has a 13-game point streak (seven goals, 13 assists) against Buffalo and 57 points (19 goals, 38 assists) in 43 games.
"You try to score every game," said Malkin, who has three goals and six assists in a six-game point streak. "It's not just against Buffalo. You just try like [heck] for the team to win. I think about every game and try to play my best."
Brandon Tanev, Jake Guentzel, Anthony Angello and Bryan Rust scored, and Tristan Jarry made 21 saves for the Penguins (16-9-1), who won their fourth straight to give coach Mike Sullivan his 300th NHL win.
"Obviously it's a humbling honor," Sullivan said. "The players gave me a nice tribute after the game. I'm just grateful to the players I've had the privilege to coach over the years, especially the guys here in Pittsburgh. We've been together here for quite some time now. … Certainly I'm the benefactor of having coached some really good players."
Tage Thompson and Victor Olofsson scored, and Jonas Johansson made 22 saves for the Sabres (6-15-4), who are 0-7-2 in their past nine games.
Pittsburgh and Buffalo played for the first time this season and play again here Saturday.
"Guys are trying but obviously it's not good enough," Sabres coach Ralph Krueger said. "We're measured by results and we've got to go back at it tomorrow and nobody's going to feel sorry for us in this situation. We've just got to fight our way out of it. Nothing's coming easy, that's for sure."
Malkin took a drop pass from Kasperi Kapanen in front of the net to put the Penguins ahead 1-0 at 6:27 of the first period.
"They're developing some real good chemistry," Sullivan said. "I think they're both really talented guys, first and foremost, and when you put them together they're real dangerous off the rush. … They've just developed a certain chemistry here over time that they've been together. We really have been encouraged by it, and I think with each game they play they get more comfortable with one another. … That tandem in particular has been dynamic."
Thompson tied it 1-1 27 seconds later, using his long reach on a wraparound to slide it under Jarry's pad at 6:54 for his first goal of the season.
"It's always nice to put one in the net," Thompson said. "Obviously, I haven't played hockey in a while, coming off the shoulder injury and then being in and out of the lineup, so it's nice to get the monkey off your back and get a little bit of confidence. But at the same time, we need to start winning games. That'll feel a lot better."