Betts finished the evening 4-for-5 with 5 RBIs and 4 runs.
He led off the game with a towering homer over the Green Monster off Yankees starter James Paxton, following up with a line shot over the Monster in the third inning and adding another in the fourth. The three-homer game from Betts marked his fourth from the leadoff spot, passing Alfonso Soriano for the most in MLB history. Betts became the eighth player in MLB history with five three-homer games, joining the likes of Alex Rodriguez, Mark McGwire, Sammy Sosa, Carlos Delgado and Joe Carter.
"It's been a long year," Betts said after the game. "Obviously not the same as last year, but you have to roll with the punches. Today was a good day. Gotta get ready for tomorrow."
With two chances to hit a fourth home run, Betts doubled in the sixth inning to drive in Michael Chavis and grounded out in the eighth. Betts said he didn't think much about the opportunity to hit his fourth homer.
"Not a whole lot," Betts said, "but in my last at-bat there, I might as well take a shot at it."
Before Friday's game, Betts met with a child from the Make-A-Wish foundation, 10-year-old Nico Sapienza, who asked him to hit a home run for him.
"I'm glad he came," Betts said. "He's our good-luck charm. He's a great kid. I think him and his family had fun down at BP. If I can use the platform I have to make people smile like that, then I know I've done something well."
"For [Betts] to walk him around and meet everybody, it was a great day for everybody," manager Alex Cora said. "I know that Mookie feels good about what happened. I don't know if he promised anything, but if he did promise, well ... it was a great night for everybody that was involved with that."
The trio of homers from Betts marked the fourth straight day a player has hit three home runs, including Mets second baseman Robinson Cano on Tuesday, Cardinals shortstop Paul DeJong on Wednesday and Twins DH Nelson Cruz on Thursday.
That extended the MLB record for most consecutive days with a three-homer game. According to Elias Sports Bureau research, when Cruz hit three Thursday, it was the first time in major league history that there had been a three-homer game on three consecutive days.
Betts' three-homer game was the 15th in MLB this season -- there were 14 each of the past two seasons.
Betts is the fourth Red Sox player to have a three-homer game against the Yankees at Fenway Park, joining Steve Pearce (2018), Kevin Millar (2004) and Mo Vaughn (1997). No player has ever hit four home runs in a game against the Yankees.