The Blues lost Nichol after he was ejected for spearing, and Colaiacovo went out with a hamstring injury in the first period. The Blues had a goal disallowed in the second period, but none of it mattered.
"I thought we really grabbed the game in the third period," new coach Ken Hitchcock said. "We played really well and with a sense of discipline. It was a hard game.
"We did a number and a job we're supposed to do, and we did it at home. Now we've got to take it on the road. It's whether we can take this same type of intensity and effort onto the road. That's the next challenge facing us."
Chris Porter had his first goal of the season, and Kris Russell added his second with St. Louis. The finished a 4-0-1 homestand under Hitchcock, who is off to the best start in club history. Leo Boivin (1976) and Jacques Demers (1984) both started 4-1.
"Whenever you lose one guy, let alone two, we did a great job of sticking together," Porter said. "Everybody was ready when they were called on. We just rolled them over."
"We've had numerous times this year where we've settled down after bad stretches, and we didn't do that tonight," Panthers coach Kevin Dineen said. "In the third period, I think they were a very hungry team. They smelled that we were trying to find an easier way to win than we've shown this year and that doesn't happen for a team."
The Blues lost Nichol, who was called for spearing Tomas Kopecky, and Colaiacovo on the same play. Hitchcock said the defenseman would be re-evaluated on Friday.
"I would prefer that I would not comment on that at this time," Hitchcock said of Nichol's penalty. "We'll just let the process take care of itself.
"I've bought a lot of boats and trailers since I've come into the league, and I prefer not to go down that path again."
Two turnovers led to a pair of first-period goals. Backes beat Theodore with a shot from the slot 6:04 in after picking off Brian Campbell's outlet pass.
Santorelli turned Jason Arnott's turnover into a goal for the Panthers, picking off the veteran's outlet pass himself and beating Halak from the left circle with a quick snap shot at 13:07.
St. Louis took the lead when Porter caught Theodore by surprise with a shot that went through his legs 5:48 into the second period.
"It was a fortunate bounce. It bounced through a few of their defensemen," Porter said. "I was just trying to get it on net. Nothing fancy. My game's not fancy. I just caught (Theodore) off-guard, I guess."
The Blues thought they had grabbed a 3-1 lead on T.J. Oshie's shot, but the goal was waved off for goaltender interference when Oshie and Florida's Jason Garrison got their skates tangled up on Barret Jackman's shot.
St. Louis went ahead 3-1 at 9:46 of the third when Russell finished off Vladimir Sobotka's crafty backhand feed at the left post.
"(Sobotka) froze that goalie on a great play," Russell said. "When a guy makes an effort like that, it's good when you can bury it for him."
Backes added an empty-netter with 1:50 to play after Florida pulled Theodore with 2:17 remaining.
"We just seemed to never get going here," Panthers defenseman Ed Jovanovski said. "Just one of those nights where you feel like you're on your heels for the majority of the night."
C Stephen Weiss, LW Tomas Fleischmann and RW Kris Versteeg, who play on the Panthers' top line, have accounted for 52 points this season. They were shut out Thursday. ... Oshie played in his 200th career game. ... Blues D Kevin Shattenkirk had a four-game point streak snapped. He has points in seven of 10 games. ... Panthers C Marcel Goc was a late scratch because of an upper body injury.