Goaltender Jake Allen made 29 saves to earn his second shutout of the season - both coming against the Blackhawks - and got offensive support from scores by Robert Bortuzzo and Alex Pietrangelo.
In his ninth start in a row, Corey Crawford had a strong game with 24 saves but suffered the loss in goal.
"I thought we competed pretty hard," Blackhawks coach Jeremy Colliton said. "We had our chances. Obviously, we would have loved to get one on the power play. Ultimately, the chances they got, I thought we turned the puck over and they were able to capitalize on it and we put ourselves in tough situations.
"But we definitely had our opportunities, we just didn't finish," Colliton continued. "I thought 'Crow' was really good. Tough. We need those two (points), obviously. But I have no complaints for the work ethic of the team."
The Blackhawks, who entered the game six points out of a wild-card spot, dropped to 31-30-8 while the Blues improved to 41-18-10.
Here are three takeaways from the Blackhawks' loss:
The Blues swept the season series 4-0, with three of the games decided by two goals or fewer.
"(They were) important games for us, a divisional rival and a team we're trying to catch up to as far as how they play and their habits," Colliton said. "There's a reason why they're leading the division. I think on the whole we haven't been good enough over the four games. We've had our stretches where we were good but not consistent enough."
Allen backstopped the Blues to a 4-0 victory on Dec. 2 at the United Center and then the Blackhawks twice coughed up third-periods leads in losses Dec. 14 and Feb. 25, both in St. Louis. On Sunday night, Allen blanked them again.
"Two of the games in St. Louis we were up for most of the game and we blew the lead," Blackhawks winger Alex DeBrincat said. "(Sunday night) was a hard battle and obviously I think it could have gone either way if we get a bounce here or there. But it's (hard). Obviously, we want to get wins and it's never good getting swept in a season series."
The Blackhawks' power play showed signs of life when it cashed in for six goals during a four-game span from Feb. 21-27 but has faltered in five consecutive contests since, including 0-for-4 on Sunday night.
"We were doing pretty well there for a little stretch," DeBrincat said. "Maybe teams are taking it away. I think we've just got to keep battling for pucks and getting pucks back. When we had success we were just putting pucks on net and it was hitting things and it was going in. Maybe we go back to that. I don't know. It's tough to swallow. Obviously, you want to convert for your team. It just didn't happen (Sunday night)."
The Blackhawks struggled with their entries against the Blues and when they did set up couldn't find shooting lanes or clog the front of the net. Chicago ended up with one shot on goal during their four power plays.
"We just have to settle down," Blackhawks captain Jonathan Toews said. "Moving around playing different positions I think you just have to relax and know where your teammates are, settle the puck down. The puck was bouncing a little bit out there, too, so it's tough to settle sometimes. We'll find a way. We just have to keep out-working that PK."
A sequence late in the second period harkened back to the old Norris Division days when gloves went flying following a hit from the Blues' Oskar Sundqvist on Blackhawks rookie Adam Boqvist.
The skaters on the ice converged along the boards and eventually, the Blackhawks' Drake Caggiula and Blues' Vince Dunn dropped the gloves and engaged in a spirited fight.
Sundqvist (elbowing and roughing), Dunn (fighting) and Mackenzie MacEachern (10-minute misconduct) drew penalties for the Blues while Caggiula (fighting) and Kirby Dach (roughing) were sent off for the Blackhawks.
The news during the intermission wasn't good as Boqvist was ruled out for the rest of the game and is in concussion protocol and Caggiula suffered a right hand injury.
After the game, the Blackhawks expressed their unhappiness with Sundqvist's hit on Boqvist.
"I think it's an unnecessary hit," Colliton said. "There's nothing wrong with finishing your check, but there was no reason, no reason for the contact to his head. It was totally unrelated to the play. It was late. (Sundqvist) was trying to get (Boqvist). So he did. And we end up losing an important player for us for the rest of the game. It puts extra stress on our defense who have played a lot, especially the top guys and we end up with a two-minute power play. It doesn't seem on the right level if you ask me."
Said DeBrincat: "(I) figured it was dirty. I saw it after on the Jumbotron. I don't know if (Sundqvist) really meant to do it, but he hits (Boqvist) in the head and you've got to be aware of your surroundings. (So you) go in there, stand up for (Boqvist) and hopefully get the team back in it."