Brandon Saad and Pavel Buchnevich scored, and Joel Hofer made 25 saves for the Blues (29-24-2), who have lost their past two games after winning eight of 10.
"We made three mistakes that cost us," St. Louis coach Drew Bannister said. "The first goal, we got caught on the wrong side of the puck. If we're under the puck there, that play probably doesn't develop. We take the penalty, they score on the power play, but that was missed coverage. The third goal's a turnover on the power play.
“We made three mistakes, and they made us pay on them."
Matthew Knies gave the Maple Leafs a 1-0 lead 22 seconds into the second period. Matthews stripped Blues defenseman Nick Leddy of the puck along the wall, fed Knies in the high slot, and the latter got past defenseman Colton Parayko before beating Hofer with a quick wrist shot.
"I just saw I had some space in the middle there," Knies said. "Once that opened up, I just wanted to throw it on the net. Luckily, it went for me."
St. Louis thought the initial entry into the zone hit a linesman or went out of play and the skaters on the ice slowed down, but there was no whistle and play continued.
"I think everyone thought that they really didn't know what the rule is," Parayko said. 'It did hit the ref, [and] I think everyone kind of thought that was going to be blown down or whatever. Maybe guys thought it went into the bench, I don't know. Just went off the ref and everyone just thought it was dead."
Saad tied it 1-1 with a power-play goal at 17:14 on a wrist shot from the slot after taking Parayko's pass from the right point.
"I just tried getting it off quickly," Saad said. "I think I felt a little pressure on my back. 'Pary' made a good play to the middle. I just tried to turn with it and get a shot off."
Matthews scored a power-play goal from the slot 45 seconds into the third period to make it 2-1, off a pass from Marner from behind the net.
The Maple Leafs were given a power play four seconds into the third after Blues forward Jordan Kyrou took a high-sticking penalty against Knies.
"The third period, again, we took charge," Keefe said. 'We buried our chance there."
Nylander scored short-handed on a 2-on-0 at 7:29 to make it 3-1 after a giveaway by Buchnevich in the offensive zone.
"I saw [Pontus] Holmberg driving backside, and I decided to shoot it myself," Nylander said. "I saw the goalie back and I shot it. It got in."