Luongo took a shutout deep into the third period before Jamie McGinn scored for the Avalanche with 8 seconds left in the game. He was busiest in the first period, turning aside all 12 shots he faced.
Santorelli scored 5 1/2 minutes into the game, putting the Canucks ahead to stay, and added his eighth of the season in the third for a 3-0 advantage.
Ryan Kesler also scored for Vancouver.
Jean-Sebastien Giguere stopped 18-of-21 shots for Colorado, which was coming off a 3-2 win over Calgary Friday.