Brett Connolly scored the go-ahead goal in the third period for the Panthers (35-26-8), who are one point behind the Toronto Maple Leafs for third in the Atlantic Division and one point behind the Carolina Hurricanes and New York Islanders in the race for the second wild card into the playoffs from the Eastern Conference.
"This obviously was a huge win for our team," Connolly said. "This is the best time of the year. There's lots of pressure now. You work hard to put yourself in position to get into the postseason. This is the time when guys are giving it a little extra. You've got to have guts. We've got to keep building. We're almost there. Just block out all the noise from everybody and play our best and see what happens."
WATCH: [All Panthers vs. Blues highlights]
Aleksi Saarela had his first two NHL assists, and Chris Driedger made 26 saves in his third straight start for Florida, which is 2-2-2 in its past six games.
"He earned his opportunity," Panthers coach Joel Quenneville said of Saarela, who played his ninth NHL game. "He made two nice plays. A great play on the second goal. He made a counter hit to free himself up and made a hard pass there to Brett."
The Blues (41-19-10), who were coming off a 2-0 win at the Chicago Blackhawks on Sunday, failed to get separation from the Colorado Avalanche in the race for first place in the Central Division. They remain two points ahead of Colorado, which lost 3-1 at the Los Angeles Kings.