Duchene had two goals and an assist, Luke Kunin had a goal and an assist and Mikael Granlund had four assists for the Predators (8-5-1), who are 7-1-1 in their past nine games. David Rittich made 33 saves in his Nashville debut.
"It's great. Nothing bothers us," Duchene said. "We were down 2-0 after the first. They were taking it to us and dominating the game really. We don't ever get too low or too high. We have fun playing. It's a very different vibe now. We keep our heads down and stay tight."
Jordan Kyrou scored twice, and Jordan Binnington made 23 saves for the Blues (8-2-2), who lost for the first time after leading by multiple goals this season.
"They're coming off a back-to-back, or this is a back-to-back for them," Kyrou said of the Predators. "Obviously they're a little juiced and we really didn't take advantage of that.
"I think in the first period, we kind of dictated the play of the game. We were forechecking hard, we were all over the puck making plays. I think the second period, we kind of let off the gas a little bit. We gave them some leeway and they scored those two goals."
Duchene took a pass from Granlund and beat Binnington with a one-timer to the short side from the right circle for the Predators.
"I was able to read off [Granlund] and score," Duchene said. "He's playing great."