Duncan Keith, Marcus Kruger, Andrew Shaw and Ben Smith tallied for the Blackhawks, who rallied from a late overtime loss in Philadelphia on Tuesday to post their second win in three outings and move into second place in the Central Division, one point up on Colorado.
The Avalanche lost, 5-4 in overtime at Winnipeg.
Ryan Miller allowed four scores on 27 shots in almost 48 minutes of action for the Blues, who lost for just the second time in the last 10 and saw their lead in the Central shrink to six points over their bitter rivals.
St. Louis picked up its first intra-division loss in 23 games (20-1-2) this season.
Notable deaths of 2014 [PHOTOS]
Michael Sam cut from the Dallas Cowboys