The Islanders won for the sixth time in eight games and ended Colorado's winning streak at three games.
Duchene stealthy left the ice when team trainers were helping injured Avs forward Blake Comeau off the ice in the middle of the first period. Duchene left the arena in the middle of the second period, briefly speaking with reporters, before jumping into a black SUV waiting outside the Barclays Center.
The Islanders scored less than five minutes into the first period on a fluky goal from Mayfield. The defenseman skated from the point down to the side of the net, where Sven Andrighetto tried to sweep the puck away but inadvertently pushed it past his own goaltender.
Bailey was credited with the primary assist on the goal and extended his points streak to nine games.
Eberle gave the Islanders a 2-0 lead when he finished off a good feed from Barzal. The goal was Eberle's third as an Islanders and the assist extended Barzal's points streak to five games.
MacKinnon scored 40 seconds into the second period, briefly pulling Colorado within one goal. Leddy scored less than a minute later to put the Islanders back in front by two goals.
Leddy scored again moments later to give the Islanders a 4-1 lead. Boychuk scored off a shot from the point at 9:46 of the second period and Eberle scored his second of the game 1:23 into the third period.
Landeskog scored Colorado's second goal at 13:02 of the second period on a scramble in front of the net. MacKinnon recorded an assist on the game extending his multi-point game streak to four.
Kerfoot scored the Avalanche's third and fourth goals in the final minute of the game.
Sunday's game against the Islanders was Colorado's final one before leaving for Sweden. The Avalanche will play two games against the Ottawa Senators in Stockholm as part of the SAP NHL Global Series.