Paul Statsny also scored and Jean-Sebastien Giguere made 28 saves for the Avalanche (7-1-0), who rebounded from their first loss of the season against Detroit on Thursday.
''We were talking in here that this team doesn't lose two in a row,'' Duchene said. ''That's the attitude we want to have so it was great to bounce back and go to 7-1.
''Right now, we're rolling, we're feeling good. We've got to get as many points as we can cause we're going to go through some adversity in the season and we've got to be ready for it and get as many points as we can while we're hot.''
Giguere said last year's Avalanche team that finished last in the Western Conference would have let a loss like Thursday's linger.
''The season we had last year, losing a game, it would have been easy to be down on ourselves, but guys were loose, they were in a good mood before the game,'' Giguere said. ''We knew that if we play the way we can play, that we had a chance.''
Buffalo finished up a stretch of four games in six days and remained winless in six home games. The Sabres did manage to score more than one goal for the third time this season.
The Avalanche scored four times in the first 32 minutes. That was more than enough against a Sabres offense that has not scored that more than three regulation goals all season.
''It was important for us to come out strong,'' Giguere said. ''We had a day off yesterday and there was no excuse for us - having young legs on the team - not to be sharp right at the beginning. And that's the sign of a team that's going in the right direction.''
The Sabres outshot the Avalanche 16-4 in the third period, but could not find the back of the net again.
''It took them almost half a game or more to get into it and we weren't our best down the stretch, but at that point, it was a hard game to play in,'' Duchene said.
Statsny scored his first goal of the season to give the Avalanche a 4-1 lead 8:34 into the second period.
Cody Hodgson put Buffalo on the board 5:31 into the second, streaking up the right side and striking a slap shot from the top of the circle past Giguere.
Duchene took a pass from O'Reilly in front of the net and converted a power play 56 seconds into the second period to make it 3-0.
Landeskog gave Colorado a 2-0 lead with 8:03 left in the first, weaving up center ice on a delayed penalty and beating Ryan Miller with a wraparound.
The Avalanche scored before the Sabres could get a shot on goal when Duchene came from behind the net and fed O'Reilly on the left side of the crease at 8:44 of the first period.
''We wanted to jump on them right away,'' Colorado coach Patrick Roy said. ''Our guys played well offensively in the first. In the second, I guess we started to back up.''
The Sabres' first shot on goal came with 5:50 left in the first period and drew a loud ovation from the crowd. Colorado outshot Buffalo 14-3 in the first period. It was the second time this season the Sabres have managed just three shots in a period.
''We have to be way, way, way better,'' Tallinder said. ''We're not playing hockey, that's for sure.''
NOTES: Buffalo added rookie D Nikita Zadorov to the active roster Saturday and sent fellow first-round pick D Rasmus Ristolainen to AHL Rochester. Zadorov can play up to nine games with the Sabres before activating his entry-level contract. . Colorado rookie C Nathan MacKinnon, the first overall pick in this year's draft, will face fellow Nova Scotia native Sidney Crosby for the first time Monday when the Avalanche play in Pittsburgh. . Miller made 22 saves for Buffalo.