The Blues, who beat Detroit 6-0 on Jan. 19, dropped their third in a row. They have lost three successive games in regulation for the first time since Feb. 27 to March 5, 2011.
Daniel Cleary and Jakub Kindl scored first-period goals for the Red Wings, who beat St. Louis 5-3 in Detroit on Friday. Cory Emmerton and Damien Brunner added second-period goals 91 seconds apart.
Mrazek, recalled from Grand Rapids on Monday, stopped the first 14 shots he faced. Jimmy Howard, the team's No. 1 goalie, was given the night off after starting the first nine games of the season.
Cleary scored on the rebound of a shot by Tomas Tatar at 5:14 of the first period. Kindl snapped a wrist shot past Brian Elliott at 11:50.
Elliott, who fell to 3-4-0, was pulled from Tuesday's 6-1 loss to Nashville after giving up four goals on 11 shots.
St. Louis defenseman Alex Pietrangelo cut the deficit to 2-1 with a power-play goal in the second period. It was the Blues' seventh power-play goal against Detroit this season.
Detroit answered 1:48 later on a goal by Emmerton. Brunner then pushed the lead to 4-1 with his fifth goal of the season.
Valtteri Filppula added an unassisted goal in the third.
Drew Miller had two assists for the Red Wings.
Flames 4, Blue Jackets 3
COLUMBUS — Alex Tanguay lost his man and found a game-winner.
Tanguay scored on a one-timer 1:07 into overtime to lead Calgary past Columbus in a battle of Western Conference cellar-dwellers.
Shortly after Columbus threatened on two shots by Fedor Tyutin, the Flames had an odd-man rush and Jarome Iginla saucered a cross-ice assist to Tanguay, who unloaded from the right dot.
Before that, however, Tanguay said he was almost the goat. He credited little-used goaltender Leland Irving, who picked up only his second career victory, for covering for him.
"Actually, it all started with Leland," Tanguay said with a chuckle. "I lost my guy in the defensive zone and they made a great play and Leland made a stop. Then (T.J.) Brodie started the play off in the corner, beat one of their guys and we were off on a 3-on-2."
Brodie, who had two assists, fed Jarome Iginla and he set up Tanguay for the winner.
"Iggy drove to the net and made a great pass to me," Tanguay said. "I just had to shoot and it was pretty much if I hit the net then I'd get a good chance to score. And the puck went in."
Roman Cervenka, Mikael Backlund and Lee Stempniak also scored for the Flames, who won their second in a row. Jiri Hudler added two assists.
Tanguay extended his points streak to seven games in a row, during which he has four goals and five assists.
The teams came into the game with the fewest points in the Western Conference, Calgary (2-3-2) was last with six and Columbus (3-6-1) was 14th with seven.
But the Flames, unlike the Blue Jackets, feel like they're shaking off their slow start.
"A gutsy effort, that's the first thing I'm going to say," coach Bob Hartley said. "We scored the first goal and they came right back. We didn't really get the first period that we wanted, but the second and third periods, we owned the puck. We made some great plays — like a great penalty kill at the end of (regulation). And then we got the winner with Tang."
The Flames were without two of their top players. Goalie Miikka Kiprusoff is listed as day to day with a leg injury. Center Mike Cammalleri, tied for the team lead in assists with five, was a game-time decision with an undisclosed injury.
Irving took Kiprusoff's place in net in just his ninth NHL game. He was making his first start since March 16, 2012, a 3-1 loss to Edmonton.
"There's nothing better. It's pretty exciting," he said after the victory. "The boys really came through tonight and played great. I'm glad they were rewarded with two points."