Colorado scored four unanswered goals and Peter Budaj made 25 saves, as the Avalanche won their second straight game, and their third out of four.
Jason Bacashihua yielded four goals on 45 shots for St. Louis, and was replaced by rookie Marek Schwarz toward the end of the second period. Schwarz had one save before Bacashihua came back onto the ice to start the third.
The Blues opened the scoring at 5:35 of the first period when Mayers scoped his fifth goal of the season.
Colorado scored three times in second period, and once more in the fourth.
Joe Sakic scored at 1:49 of the second and Stastny scored less than two minutes later on a feed from Turgeon. At 15:10, Hejduk made it 3-1 with his 10th goal of the season.
Turgeon wrapped up the scoring with his third goal of season at 5:45 of the third.