The Avalanche were 39-13-4 with 82 points to finish tied with the Vegas Golden Knights (40-14-2) but had more regulation wins (35-30).
Colorado will play the St. Louis Blues in the Stanley Cup First Round and will be the top seed for as long as they remain in the playoffs.
"It feels good," Avalanche forward Mikko Rantanen said. "We achieved the first goal we had this year, to get the home-ice advantage for the whole playoffs and we checked the one box. Everybody knows what the next box is, so we have to start working on that. I believe in this group. Our goal is to go all the way to the end."
It's the third time the Avalanche have won the Presidents' Trophy since it was first awarded in 1985-86. They did so in 2000-01, when they defeated the New Jersey 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.
"The playoffs are a different animal, everybody knows that," Colorado coach Jared 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."
Colorado had four winning streaks of at least five games, including a season-high seven-game streak from March 10-22, which began a stretch when they were 18-1-2. The Avalanche lost consecutive games in regulation three times.
"I love the way we finished the season," Bednar said. "I love the way guys dug in, guys stepping into different roles, different guys chipping in every night. We won some ugly games, we won some games where we played real well. There were a lot of contributors most nights."
The Avalanche lead the NHL in goals per game (3.52) and are in the top five in goals against per game (2.36).
Rantanen led the Avalanche with 66 points (30 goals, 36 assists). Center Nathan MacKinnon scored 65 points (20 goals, 45 assists), and forward Gabriel Landeskog was third with 52 points (20 goals, 32 assists).
Goalie Philipp Grubauer (30-9-1, 2.21 goals-against average, .922 save percentage) was second in the NHL in wins behind Andrei Vasilevskiy of the Tampa Bay Lightning (31) and tied for first in shutouts (seven) with Semyon Varlamov of the New York Islanders.
Of the 34 previous teams to win the Presidents' Trophy, eight have won the Stanley Cup; the Chicago Blackhawks were the last to do so in 2012-13. Three others lost in the Stanley Cup Final; seven lost in the first round and 16 lost in either the second round or conference final.
Last season, the Boston Bruins won the Presidents' Trophy and lost to the Tampa Bay Lightning in five games in the Eastern Conference Second Round.
NHL.com independent correspondent Rick Sadowski contributed to this report
