The Blues had lost three straight (0-2-1) since the defenseman experienced a cardiac episode Feb. 11 at the Anaheim Ducks, and five overall (0-3-2).
Jordan Binnington made 17 saves for his second shutout of the season, and Ivan Barbashev scored twice for the Blues (33-17-10), who have won 12 straight against the Devils and eight in a row at home.
"No. 1, it feels good to be back in the win column as a team," Binnington said. "I think it's important that we went through that and continued to believe in ourselves and grow and stick to the plan and just stay calm. It's a great 60-minute game by us tonight. Hopefully we can continue that going forward."
WATCH: [All Devils vs. Blues highlights]
Louis Domingue made 36 saves for the Devils (22-27-10), which had a point in eight of their past 10 games (5-2-3).
"They outplayed us. It's a good team," Devils forward Kyle Palmieri said. "They've won a lot of games for a reason, and they had a game plan and they stuck with it. I thought the first 10 minutes of the game we're moving, we're quick with our decisions and making simple plays and got away from that, and a good team like that's going to take advantage.
"We didn't defend hard enough. We weren't ending plays. Louie stood on his head for us and we didn't give him much support."
Barbashev scored at 9:21 of the second period to for a 1-0 lead when he converted from the slot after Carl Gunnarsson's shot caromed off Devils defenseman Damon Severson.
"I think there was a good change by [Zach] Sanford, first of all. Good forecheck by [David Perron], and [Robert] Thomas, I think it was, got the puck back and Carl found me," Barbashev said. "I had bad hands, puck bounced the other way, but I got lucky."