The Blues scored three times in the first 9:45 to jump in front 3-0 and chase Nashville goalie Pekka Rinne.
Jaroslav Halak made 28 saves for the Blues and improved to 9-3-3 against the Predators.
St. Louis has won four of its past five home openers.
Nashville, which missed the playoffs last season, is 7-7-1 in season openers.
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