Vegas leads Colorado by six points for first place in the Honda West Division. Each team has already clinched a berth in the Stanley Cup Playoffs.
"Huge result for the standings," Golden Knights coach Peter DeBoer said. "We've still got a lot of business to take care of over the next two weeks. It sets us up where our destiny is in our own hands."
Max Pacioretty had two goals and an assist, and Mark Stone had a goal and two assists for the Golden Knights (35-11-2), whose streak is the longest in their history. Marc-Andre Fleury made 35 saves for his 488th win, one shy of tying Roberto Luongo for third in NHL history.
"Still a lot of the season to be played," Pacioretty said. "With eight games left, we know we're in a good position right now. However, we know we have to play better when they have their full lineup."
Devon Toews and Ryan Graves scored for the Avalanche (31-12-4), who have lost three in a row after winning their previous five. Devan Dubnyk made 21 saves.
"Losing three straight isn't something we're familiar with very often here," Toews said. "This little stretch we know isn't going to last."
Colorado leads the Minnesota Wild by one point for second place in the division.
"You look at these three teams and they're all really good hockey teams," Avalanche coach Jared Bednar said. "There's six points between us could have been smaller if we had won. I think [Vegas] is a real good hockey team and can win on any given night."
William Karlsson scored 10 seconds into the game to give the Golden Knights a 1-0 lead. It was the fastest goal to start a game in team history; Karlsson scored 14 seconds in against the San Jose Sharks on Nov. 24, 2018.