Raimel Tapia also connected for the Blue Jays, who clinched an AL wild-card berth Thursday when the Red Sox beat the Baltimore Orioles. Toronto had a clubhouse celebration after the game Friday.
''This party was scheduled whether we won or lost,'' Manoah said. ''For me, the biggest thing was let's have a good time, but with a win.''
Toronto pounded out 13 hits in its ninth shutout win of the season.
''You can't really write it any better,'' interim manager John Schneider said.
Toronto (88-69) leads the AL wild-card race, ahead of Seattle and Tampa Bay. The Blue Jays went 18-10 in September. They're 14-3 against the Red Sox this season.
''They're changing rules, not divisions,'' Boston manager Alex Cora said. ''We're going to face all these teams and we've got to do a better job. They've had their way against us.''
Boston is 23-48 against AL East opponents. The Red Sox (75-82) are assured of their first losing record in a 162-game season since going 78-84 in 2015. Boston went 24-36 in the pandemic-shortened season of 2020.
Guerrero hit a two-run shot off Canadian-born right-hander Nick Pivetta (10-12) in the third inning, his 31st. Tapia homered off Tyler Danish to begin the sixth, his seventh. Three batters later, Springer hit a three-run homer, his 25th.
Manoah (16-7) allowed two hits, struck out four and walked two, his eighth consecutive start allowing two earned runs or fewer. The right-hander has won his past four decisions, and his ERA of 2.24 is fourth-lowest in the majors.
''He's really good,'' Red Sox manager Alex Cora said. ''With him, it's not six innings, three runs. It's six innings, one run. You see the ERA, you see the numbers, he's been a horse for them.''
Manoah didn't allow a hit through the first four innings, but Abraham Almonte reached on a one-out single in the fifth when Manoah was late breaking for first base on Almonte's grounder down the first base line.
''I read it wrong,'' Manoah said. ''I thought it was foul by a wide margin.''
The next two Red Sox batters flied out.
Jarren Duran reached on a bloop single to begin the sixth, but Rafael Devers followed by grounding into a double play.
Left-hander Yusei Kikuchi pitched the final three innings for his first career save.
''That's really cool for him,'' Schneider said. ''You saw the bullpen, they were up on the fence wanting him to do it.''
Blue Jays shortstop Bo Bichette went 2 for 4 with a walk, giving him 48 hits in September. It's the most ever by a Blue Jays player in a calendar month, breaking Tony Fernandez's mark of 47 hits in June 1986.
Pivetta allowed four runs, three earned, and six hits in five innings as Boston lost for the first time in four games.
''The breaking ball wasn't there today,'' Cora said. ''The fastball towards the end was good but I felt like the whole night he wasn't able to have his curveball.''
Boston put unvaccinated RHP Kaleb Ort on the restricted and recalled Duran from Triple-A Worcester.
Ort is expected to join the Red Sox in Toronto on Saturday, the first day of October, with the expiration of a Canadian requirement that prevents foreign nationals who aren't vaccinated against COVID-19 from entering the country.
GOT IT ALL
Guerrero's homer went 447 feet and had an exit velocity of 117.5 miles per hour, making it the second hardest-hit home run of his career. On April 10 against Texas, he hit one that came off the bat at 117.9 miles per hour. Friday's second-deck blast was the hardest-hit home run allowed by a Red Sox pitcher since the introduction of Statcast in 2015.
''It looked like a line drive in the gap and then it just kept going,'' Manoah said. ''It was crazy.''
RHP Brayan Bello (2-7, 4.39 ERA) starts for the Red Sox on Saturday against Blue Jays RHP Ross Stripling (9-4, 3.16 ERA). Bello posted a 1.65 ERA in five September starts.
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