The Ducks outshot Colorado 14-9 in the second stanza, but the Avalanche made opening night a difficult one for Anaheim goaltender Viktor Fasth.
Colorado had a 1-0 lead heading into the second and Downie started the onslaught with a power-play goal 8:38 into the period. John Mitchell scored just over two minutes later and Jamie McGinn gave Colorado a 4-0 cushion with 2:40 to play.
McGinn scored again midway through the third, becoming one of four players in the NHL to produce a pair of goals over the opening two nights of the season.
Semyon Varlamov saw his bid for a shutout spoiled with seven seconds left in the third period on a goal by Jakob Sifverberg.
Varlamov turned aside 35 shots and Fasth gave up all six goals on 29 shots.