O'Reilly got the Avalanche its first goal of the night at 8:44 of the first period. Duchene set up O'Reilly with a pass in front of the net, where he was all alone with time to beat Sabres goalie Ryan Miller (22 saves).
"[Duchene and O'Reilly] have been dominant, to be honest with you," Avalanche coach Patrick Roy said. "What I like about them is the consistency that they're bringing every night. That's a good sign of maturity. They start to get mature and they show a lot of poise and good things out there."
Landeskog would make it 2-0 in the first at 11:57 scoring on a wraparound goal. The Avalanche lead would grow to 3-0 just 57 seconds into the second, when Duchene beat Miller on the power play after tipping O'Reilly's shot in front.
"I don't know. It might've hit me," Duchene said with a smile while explaining the goal. "It doesn't matter either way; I'm not too worried about it. If I got it, they'll give it to me, if not, they won't. It was the winning goal for us and that's all that matters."
The Avalanche held the Sabres without a shot for the first 14 minutes of the game and getting off to a good start was one of the things they keyed in on heading into Saturday's game.
"That's what we wanted. We talked about it this morning, we talked about it before the game," Roy said. "We needed a good start and that's exactly what we got from our guys. Third goal and fourth goal were big for us at the same time."
The Sabres made it a 3-1 game when Cody Hodgson fired a slap shot past Jean-Sebastien Giguere (28 saves) at 5:31 of the second. Thomas Vanek hit Hodgson with an outlet pass and Hodgson let his shot go from just outside the faceoff circle.
Paul Stastny made the score 4-1 with his first goal of the season at 8:34 of the second period.
The Sabres would cut the lead to 4-2 at 1:05 of the third, when Marcus Foligno scored on a scramble around the net. The Sabres would pressure the Avalanche in their end for the better part of the period, but were unable to beat Giguere again.
The Avalanche were coming off its first loss of the season on Thursday night to Detroit.
"We were talking in here that this team doesn't lose two in a row and that's the attitude we want to have," Duchene said. "It was great to bounce back and go to 7-1. We're rolling, we're feeling good."
For the Sabres, Saturday's loss was their second in a row and ninth in the past 10 games.
"There's too much thinking, maybe, instead of just doing. Or maybe it's not enough thinking. You pick and choose. It's very hard to say," Sabres defenseman Henrik Tallinder said. "I think we're tentative at times. Even when we chip it out of our zone, they get the puck back. They can come in 3-on-2s, almost breakaways. That means we're doing something wrong as a team. What it is is a good question. But it comes down to playing hockey. ...We're not playing hockey, that's for sure."
The Avs will now head to Pittsburgh for a Monday night matchup against the Penguins. Both teams are atop the league standings with 7-1-0 records.