Sam Malinski had a goal and an assist, and Scott Wedgewood made 29 saves for the Avalanche (47-13-10), who have won three in a row.
Kris Letang had an assist to reach 800 NHL points, and Egor Chinakhov and Rickard Rakell scored for the Penguins (35-20-16), who have been outscored 11-3 in two straight losses. Arturs Silovs made 24 saves.
Nathan Mackinnon put Colorado ahead 1-0 at 4:57 of the first period on his 46th goal this season. He poked the puck away from Parker Wotherspoon at the opposite blue line and held off the Pittsburgh defenseman on a partial breakaway for a wrist shot glove-side.
Chinakhov scored in a third consecutive game to tie it 1-1 at 8:09 with a one-timer from the point set up by Samuel Girard.
Malinski, Necas and Parker Kelly later scored three goals in 1:55.
Malinski gave the Avalanche a 2-1 lead at 15:24 with a wrist shot in off the left post.
Necas made it 3-1 five seconds into a power play at 16:44 on a one-timer from the left face-off circle set up by Cale Makar.
Kelly dropped to a knee for another one-timer, extending the lead to 4-1 at 17:19.
Justin Brazeau seemed to score for the Penguins at 7:38 of the second period, wrapping a rebound around Wedgewood, but the Avalanche challenged and it was determined he interfered with Wedgewood.
Pittsburgh then had two shots on goal during a four-minute power play after Nazem Kadri was called for high-sticking at 8:25.
Necas pushed the lead to 5-1 at 17:29 on Colorado’s third shot on goal of the second, a wrist shot off a rebound from Devon Toews.
Rakell tapped in a pass from Sidney Crosby to cut it to 5-2 at 11:47 of the third period.
Ross Colton scored an empty-net goal at 16:20 for the 6-2 final.