The new mark moved Boston past the 105 games the 1912 team won en route to winning the World Series, though that was in a 154-game schedule. The Sox's victory Monday came in their 157th game of the year.
The Red Sox were still shaking hands on the field when the "106" went up in the win column of the American League East standings that are posted on the Green Monster. Scoreboards flashed "106 Wins" and fans waved signs to celebrate breaking a record that has stood as long as Fenway Park itself.
"You think about all the history of the game and the history of this franchise," Boston manager Alex Cora said.
The victory also assured the Red Sox of home-field advantage throughout the postseason, as it put Boston out of reach of the AL West-leading Houston Astros.
Historically, securing the best record in baseball bodes well for the Sox, who won the World Series in five of the six years when they owned at least a share of the top record (1903, 1912, 1915, 2007 and 2013). They lost the Fall Classic in 1946 in seven games.
Cora said he asked injured second baseman Dustin Pedroia, as the longest-tenured member of the Sox, to speak to his teammates after the game to reflect on the accomplishment.
"To be part of this, I can't even explain it. We should call timeout and enjoy this one," Cora said. "We know what we want to do in October, but this one ... for us to do it is amazing."
The team with the best record has reached the World Series in both of the past two seasons: The Cubs won it all in 2016, and the Dodgers lost in Game 7 last year.
The Sox could set one more record in the regular season for Cora. Boston is only three wins from tying the 1961 Yankees for the most wins by a rookie skipper's team.
Cora, who was wearing a shirt with a stylized Puerto Rico flag, smiled about the impact of his success on his native Puerto Rico.
"I'm the second Puerto Rican to ever manage in the big leagues; you guys know how I feel," he said. "That's why I have this [shirt]. For this to happen is very special. We sit down at home and sometimes we're in awe, like, 'This is really happening.'"