The trio combined for 10 points, with Perron recording his first NHL hat trick, Boyes netting a goal and three assists, and McDonald contributing a goal and two assists in his 500th career game.
It added up to St. Louis' 6-1 victory over the Vancouver Canucks on Tuesday night.
The Blues, who were 1-5-1 in their first seven home games, scored four times in the first 7:36 - including Perron's two goals in a span of 1:54.
"We hadn't played real well at home," said Boyes, who nearly matched his season total of six points. "It was a tough building to play in last year. We've got to get that way again. This was a good way to get going."
Erik Johnson also scored, and Chris Mason made 22 saves for the Blues.
"We wanted to be good early, and that was the message," Blues coach Andy Murray said. "Tonight, we were good early."
The Canucks, who had won three of four, got a third-period goal from Henrik Sedin.
"They beat us to loose pucks, they were the better team 1-on-1 and they had better chances obviously," Canucks coach Alain Vigneault said of the Blues. "They played real well. That team came out real hard. Their execution was real good and they took it to us real hard in the first period. They had some quality chances and they buried them."
Andrew Raycroft, who had been 4-1 with a 1.60 goals-against average while No. 1 goalie Roberto Luongo was injured, allowed four goals on 13 shots before being replaced after the first period.
"Obviously it was a tough first period," Raycroft said. "Four goals in eight minutes is not good enough."
Luongo then made his first appearance since Oct. 27, when he broke a rib. He was not expected to play until Thursday in Detroit.
"That's the only positive thing," Luongo said. "I got some minutes, but it's tough. You don't want to come in situations like that."
McDonald scored 18 seconds into the game, beating Raycroft with a wrister from the slot after a drop pass by Boyes. Perron's deflection in the slot of Boyes' shot from the top of the left circle at 5:42 made it 2-0.
"We came out pretty hard," McDonald said. "We generated a lot of chances in the first. It's something we've failed to do in the past. We've been struggling to score goals, so it was nice to be able to come out and jump on them a little bit and get everybody rolling."
Johnson, who missed last season due to a knee injury, scored his first goal since March 28, 2008, when his feed into the slot deflected into the net off Canucks winger Matt Pettinger's skate at 6:53.
Perron netted his sixth of the season by sending in a wrist shot from the right circle at 7:36, giving the Blues a 4-0 lead.
Boyes' third of the season came on the power play, a one-timer from the left circle off a feed from McDonald past Luongo at 18:45 of the second period.
Sedin broke Mason's shutout bid 1:02 into the third when his backhander trickled over Mason and across the goal line after the goalie was picked by Ryan Kesler behind the net.
Perron completed his hat trick when he deflected in Johnson's shot 15:53 into the third.
"It's always good to get a goal, and it's even better to get two, and even better to get three," Perron said. "The most important thing was we got a lot of shots. We got some goals, finally, so it felt good."
NOTES: It was the first meeting between the teams since the Canucks swept the Blues in the first round of the playoffs last season. ... The Blues' four goals in the first 10 minutes marked the third time they've accomplished such a feat. The team record for quickest four goals at the start of a game is 6:41 set on Feb. 6, 1973, against the Canucks. ... Vancouver LW Daniel Sedin (broken foot) was on the ice Tuesday morning but didn't play. Sedin, sidelined since Oct. 10, could be in the lineup Thursday at Detroit. ... Blues LW B.J. Crombeen and Canucks D Kevin Bieksa fought each other twice. ... The Blues are 3 for 35 on the power play in eight home games after going 2 for 7 Tuesday.
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