The Avalanche, who beat Dallas on Thursday in their preseason opener, got goals from Chris Stewart and Matt Duchene, the third overall pick from the 2009 draft.
Goalie Ty Conklin, signed as a free agent by the Blues in the offseason, made his debut with the team and stopped 21 shots through two periods before being replaced by Jake Allen. Colorado's Tyler Weiman played the entire game and stopped 30 shots.
Drazenovic scored 9:39 into the first period on a one-timer from the left circle and Kariya, who skated in his first game Tuesday in nearly a year following surgeries on both hips, notched his second goal in as many games 12:26 into the opening period.
Steen was given credit for the Blues' third goal of the period at 15:02 when Colorado's Wojtek Wolski inadvertently backhanded the puck into his own net trying to clear it around the boards.
The Blues led 4-0 on Oshie's goal at 4:18 of the second before Stewart got the Avalanche on the board with 1:08 remaining in the period.
Copyright by STATS LLC and The Associated Press
Arena: Scottrade Center Location: Saint Louis, Missouri
Attendance: 10,042 (52.4% full)
Nicholas Drazenovic Assist: Julian Talbot, Derek Armstrong
Paul Kariya Assist: Keith Tkachuk, Erik Johnson
Alex Steen Unassisted
T.J. Oshie Assist: Brad Winchester, Patrik Berglund
Chris Stewart Assist: Matt Duchene, Kyle Cumiskey
Matt Duchene Unassisted
Brandon Crombeen Assist: Jay McClement, Alex Steen
Derek Armstrong Assist: Keith Tkachuk, Paul Kariya