Gabriel Landeskog had a goal and two assists, Nathan MacKinnon had a goal and an assist, and Jonathan Bernier made 32 saves for Colorado (43-30-9), which ended a three-game losing streak.
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"I don't know what the odds were for us to win tonight, but we didn't give a (darn), to be honest with you," Landeskog said. "We just kept playing, and what a night. This is one heck of a group. I don't think I've ever been a part of a group with such team chemistry. Whether we made it or not, I'd still be really proud of this group. This is a big accomplishment to make it after such a tough season last year. We're not done."
The Avalanche made the playoffs for the first time since 2013-14 after finishing with an NHL-worst 48 points last season.
"It's got to be one of the best accomplishments in modern sports history," MacKinnon said. "We came in last by 20 points, we were the worst team in 25 years. We did the unthinkable. It's obviously a huge deal."
Jaden Schwartz and Brayden Schenn each had a goal and an assist, and Jake Allen made 34 saves for the Blues (44-32-6), who lost five of their final six games (1-4-1).
"There's a lot of people, a lot, I mean, majority of people who didn't even give us a chance to be in this game, to be here," Allen said. "We had our ups and downs this year, it was a wild year. But we rallied and found a way to beat good teams at the right time and give ourselves a chance.
"Credit to Colorado, they've improved immensely over the last couple of years and they played well again tonight, obviously. It's tough to take. We gave ourselves a chance, but it was still not good enough."