The Avs now lead the best-of-seven set 2-1, with Game 4 slated for Wednesday back at the Pepsi Center (8 p.m. CBC/Sportsnet, Sportsnet 906 THE FAN).
Cale Maker, Matt Nieto, Mikko Rantanen and Erik Johnson also had goals for the homeside, while Sam Bennett and T.J. Brodie scored for the Flames.
Mike Smith had another outstanding outing, stopping 50 of 56 shots.
"We got down early and basically played high-risk hockey for the rest of the night, and they made us pay every time," said captain Mark Giordano. "That's obviously not even close to where we want to be when you give up that many shots.
"And they had a lot of quality looks.
"We've got to re-group here and stick together as a team, but we know that our compete level, No. 1, has to go way up. We've got to be smarter with our decisions with the puck, our pinches, everything. Everything across the board. There wasn't much good, honestly, throughout the night. (We) made that team look and feel good all night.
"We need to come back, re-group, and we need to win this next one."
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The Avs entered the night 0-for-8 on the powerplay through the first two games in the series, but quickly ended the oh-fer drought with a pair of strikes to open up an early, two-goal lead and set the tone for the evening.
The first came on a full, two-minute 5-on-3 as Oscar Fantenberg sat for hooking, while a bench minor for too-many-men was also assessed on the same sequence.
MacKinnon walked off the right circle and - with Colorado captain Gabriel Landeskog setting the screen in front - he wired a shot over the shoulder of Smith to give the Avs a 1-0 lead.
Then, with Garnet Hathaway serving a holding penalty, MacKinnon scored the second of two goals in the frame, one-timing a pass from Rantanen short-side on Smith to make it a 2-0 game at 13:34.
Head coach Bill Peters - who otherwise liked the start the Flames had, showing all kinds of jam early and cracking a post on a powerplay less than five minutes in - said his team was "chasing" from that point on.
"They're doing a good job playing with pace and we're spending too much time in our own zone because of it," he said.
"It's us feeding their transition game and getting beat up ice and we're having some trouble sorting it out, obviously, and because of that, they're getting a lot of odd-man rushes.
"If I could pick an area to clean up, that would be our No.-1 priority."
