The Blue Jays scored four runs in the first inning en route to their fourth win in seven games.
Toronto starter Yusei Kikuchi (6-2) gave up a two-run homer to William Contreras in the opening frame but settled in after that, allowing just three hits over five innings.
The left-hander issued five walks and had four strikeouts, including the 500th of his career.
Cavan Biggio and Merrifield each had a pair of hits for the Blue Jays in the opener of the three-game series.
Brewers starter Adrian Houser (1-1) lasted 4 1/3 innings, allowing six earned runs, 11 hits and three walks. He had three strikeouts.
With the roof open on a glorious spring evening, the Blue Jays gave the Rogers Centre crowd of 32,930 something to cheer about in the early going.
Guerrero and Matt Chapman delivered RBI singles in the first inning and Merrifield sent a roller down the third-base line to bring home two more runs.
The Blue Jays loaded the bases with nobody out in the second. Kirk scored on a fielder’s choice and Brandon Belt added an RBI single.
Toronto right-hander Nate Pearson had four strikeouts over two shutout innings. Adam Cimber, Tim Mayza and Yimi Garcia also made relief appearances.
The game kicked off a seven-game road trip for the Brewers (28-26), who lead the National League Central Division standings.
The Blue Jays (29-26) have a better record but started the day in last place in the powerhouse American League East.
Baseball’s hits leader, Bo Bichette, had his eight-game hitting streak come to an end. He was the only Toronto starter without a hit.
Milwaukee shortstop Andruw Monasterio singled in the second inning for his first big-league hit. The Blue Jays outhit the Brewers 14-4.
The game took two hours 31 minutes to play.
Blue Jays outfielder Kevin Kiermaier was not in the starting lineup as he continues to deal with lower back discomfort.
Toronto manager John Schneider said Kiermaier has made progress over the last few days. Kiermaier hasn’t played since he was removed from a game Saturday at Minnesota.
It was the first game at Rogers Centre for Brewers slugger Rowdy Tellez since he was traded from Toronto to Milwaukee two years ago.
Tellez spent parts of four seasons with the Blue Jays, who drafted him with the 895th overall pick in 2013.
Right-handers were set to square off on Wednesday night with Julio Teheran (0-1, 1.80 earned-run average) to start for the Brewers against Alek Manoah (1-5, 5.53).
Toronto’s Kevin Gausman (3-3, 3.03) was tabbed for the series finale on Thursday against fellow righty Freddy Peralta (5-4, 4.64).