Colorado (39-13-4) won the Honda West Division and will have home-ice advantage against fourth-place St. Louis (27-20-9) in the best-of-7 series.
Game 1 is at Colorado on Monday.
"When we're skating and we're physical, I think we give them a lot of issues," St. Louis captain Ryan O'Reilly said. "Whether that's forecheck or defending. When we play our heavy game and commit to it and put pucks in and don't feed their rush, we make it tough on them and find ways to beat them. That's what we've got to do. That's got to be our focus. We know that they have a lot of talent over there. They work hard, but for us, it's an exciting challenge. We're going to have some fun and we're going to beat them."
The Avalanche were 5-3-0 against the Blues, with each win in regulation.
"This is going to be a tough challenge, the playoffs," Colorado coach Jared Bednar said. "You look at the field and the teams that are in it, there's not a team that anyone can take lightly. Everyone has the ability to win this thing."
Forward Nathan MacKinnon led the Avalanche with 14 points (six goals, eight assists) against the Blues. Defenseman Cale Makar was second with 10 points (two goals, eight assists), and forwards Andre Burakovsky (four goals, five assists) and Gabriel Landeskog (three goals, six assists) each scored nine points. Philipp Grubauer was 2-1-0 with a 1.68 goals-against average, a .938 save percentage and one shutout against St. Louis. Devan Dubnyk was 2-1-0 with a 3.04 GAA and a .900 save percentage, and Jonas Johansson was 1-1-0 with a 3.00 GAA and an .872 save percentage.
"We know they're a good team, we have a good rivalry against them," Colorado forward Tyson Jost said. "We've had some great battles in the past. It's been a battle these last three, four years. They've had success against us in their building, but we're excited. It's going to be a good matchup and we know what to expect. It's a veteran team out there and we're going to have to come out hard and be prepared."
O'Reilly (four goals, three assists) and forward David Perron (two goals, five assists) each scored seven points against the Avalanche to lead the Blues. Forward Mike Hoffman scored six points (four goals, two assists). Jordan Binnington was 3-4-0 with a 2.89 GAA and a .909 save percentage against Colorado, and Ville Husso was 0-1-0 with a 4.53 GAA and an .875 save percentage in two games (one start).
"At the end of the day, we knew we had the team on paper to put this thing together and get into the playoffs and that's what we did," St. Louis forward Brayden Schenn said. "We're playing, what it looks like, a good, solid Colorado team and we're ready for the challenge obviously. We're coming in as underdogs and we like that."
Rantanen led the Avalanche with 66 points (30 goals, 36 assists). MacKinnon scored 65 points (20 goals, 45 assists), and Landeskog was third with 52 points (20 goals, 32 assists).
Grubauer was 30-9-1 with a 1.95 GAA, a .922 save percentage and six shutouts. Jonas Johansson was 5-1-1 with a 2.06 GAA, a .913 save percentage and one shutout since being acquired in a trade with the Buffalo Sabres on March 21, and Devan Dubnyk was 3-2-0 with a 3.26 GAA and an .886 save percentage since being acquired in a trade with the San Jose Sharks on April 10. Hunter Miska was 1-1-2 with a 4.16 GAA and an .838 save percentage but did not play after March 16.
The Blues were led in scoring by Perron (58 points; 19 goals, 39 assists) and O'Reilly (54 points; 24 goals, 30 assists). Schenn (36 points; 16 goals, 20 assists), Mike Hoffman (36 points; 17 goals, 19 assists) and Jordan Kyrou (35 points; 14 goals, 21 assists) were the other forwards to score more than 30.
Binnington was 18-14-8 with a 2.65 GAA and a .910 save percentage in 42 games (41 starts), and Husso was 9-6-1 with a 3.21 GAA and an .893 save percentage in 17 games (15 starts).
"We played them well at times this year, and the other times, they put it in the back of our net quite easily if we don't do the right things," Perron said. "There's going to be a lot more intensity, a lot more details that are required to have success. We know what kind of firepower they have over there. Also being disciplined. Our power play's been coming around more and more as the year's gone on, but we also know how good they are on their side and we'll have to be really sharp."
This will be the second time the Avalanche and Blues meet in the playoffs. Colorado defeated St. Louis in five games in the best-of-7 Western Conference Final in 2001, on the way to winning the Stanley Cup.
Colorado, which has qualified for the playoffs four straight seasons, lost to the Dallas Stars in seven games in the Western Conference Second Round last season.
St. Louis, which qualified for a third straight season, lost to the Vancouver Canucks in six games in the best-of-7 Western Conference First Round last season. The Blues won the Stanley Cup in 2019.
"We're going to go through some big battles here to keep having success, and there's not many people probably around the world that's giving us much of a chance, but we know what type of a team we have in here," Perron said. "We've had success before."
The Avalanche had the best record in the NHL to win the Presidents' Trophy for a third time. They also did so in 2000-01, when they defeated the Devils in seven games to win the Stanley Cup, and in 1996-97, when they lost to the Detroit Red Wings in six games in the Western Conference Final.
Colorado will be the top seed for as long as they remain in the postseason.
"The playoffs are a different animal, everybody knows that," Bednar said. "No one's going to look at us and say, 'Yep, they won the Presidents' Trophy, they're going to roll over everyone.' It's not going to happen. It's going to be a tough grind. It can put a target on your back, but we have to be comfortable with that. We set high expectations and I don't think we should shy away from trying to achieve them, and the Presidents' Trophy is one of them."
The series winner will play the winner of the series between the Vegas Golden Knights (No. 2) and Minnesota Wild (No. 3) in the second round.
"These games throughout the season, these games have been so intense and so competitive," O'Reilly said. "It's fun though. It's going to be an intense battle. I want to beat them bad."
NHL.com independent correspondents Louie Korac and Rick Sadowski contributed to this report