Cody Glass and Michael Bunting scored for the Penguins (12-14-4), who have lost two of three after winning their previous four. Tristan Jarry made 21 saves.
“I didn’t think we were as stiff on the puck,” Pittsburgh coach Mike Sullivan said. “I thought we hung onto pucks more in the offensive zone. I thought we could’ve controlled territory a little bit more and forced them to have to defend us a little bit more.”
MacKinnon put the Avalanche ahead 1-0 on their second shot on goal at 6:31 of the first period, driving through the neutral zone to the left face-off circle for a snap shot and his 10th goal this season.
Rantanen ended a five-game goal drought when he made it 2-0 at 18:22. After Cale Makar tipped the puck away from Kris Letang in the left circle, he slid it to Rantanen who chipped it in off Jarry's right pad.
Rantanen then extended the lead to 3-0 at 5:46 of the second period by dropping to one knee for a one-timer from a sharp angle.
“They’re overall really good players, you know?” Letang said. “MacKinnon has the speed, the skill, the shot. Rantanen has a big presence. He’s really good around the net. It’s tough to knock them off the puck. And then you add Makar, he’s probably one of the top players in the game right now. He just makes the other team look silly.”
Glass cut it to 3-1 at 7:21 on his first goal of the season, a wrist shot from the right circle off a pass from Evgeni Malkin.
Bunting pulled the Penguins to within 3-2 at 18:53, taking a spinning pass from Erik Karlsson for a wrist shot from the slot.
Nichushkin powered his way to the net around Marcus Pettersson and slipped the puck by the right skate of Jarry, extending the lead to 4-2 at 3:23 of the third period.