Makar made it 3-1 at 12:37 of the second, beating Fleury five-hole after cutting inside Golden Knights defenseman Nick Holden.
Landeskog increased the lead to 4-1 at 15:41. Mikko Rantanen deflected Makar's point shot, and Landeskog found the loose puck near the right post.
Pierre-Edouard Bellemare converted a cross-ice pass from Compher on a rush at 3:54 of the third period to make it 5-1.
"I thought it was a grind for our guys tonight," Colorado coach Jared Bednar said. "The Bellemare line was outstanding, the [Tyson] Jost line was also good, and we found a way to score some timely goals and check pretty hard and played with pretty good pack mentality, but the game was a little bit sloppy, and I just didn't think we had a lot of energy."
Nicolas Roy scored for Vegas at 14:36 of the third, but Bednar challenged the play for offside, and the goal was waved off after video review showed Ryan Reaves entered the Colorado zone ahead of the puck at 14:27.
"I don't think you can move on when you lose a game 5-1," Golden Knights captain Mark Stone said. "You have to sit down and look at it and see what went wrong. At first glance, kind of got out-competed. The first period was pretty level. Take three penalties in the first [10] minutes of the second period, lose flow, lost a lot of our top guys sitting. The penalty kill did a great job, and they get a lucky goal. Just took a lot of flow out of the game, and they completely dominated us for the last 15 minutes of that period."
NOTES:It was the first loss for Vegas this season when leading entering the second period (14-0-0 entering Thursday). … It was Bednar's 166th win with Colorado (166-144-38), moving him past Marc Crawford for third place in wins by a coach in Avalanche/Quebec Nordiques history. He trails Michel Bergeron (265) and Bob Hartley (193). … Rantanen has 14 points (seven goals, seven assists) during an eight-game point streak. … Landeskog has 13 points (four goals, nine assists) during a seven-game point streak and moved past Alex Tanguay (488 points) into eighth place in points in Avalanche/Nordiques history. … Colorado wore "Boulder Strong" warmup jerseys with the No. 10 to honor the 10 victims of a mass shooting at a supermarket in Boulder, Colorado, on Monday. The jerseys will be signed and auctioned off with the proceeds going to the Colorado Healing Fund.