"Yeah, I was just trying to look for a good pitch," said Sizemore. "I wasn't really sitting on anything. I was just trying to hit the ball over the plate and get something good to hit."
Entering the top of the sixth, the Red Sox had only come up with one hit on the night, marking three straight games they had one hit in the first five innings.
But Jonny Gomes tied the game by leading off the sixth with a shot against CC Sabathia.
"CC is such a competitor and bulldog out there," said Gomes. "Once he gets the lead, you have to do what you can to jump him. So coming out in the sixth, he's going to be pounding the strike zone. So I want to try and be aggressive in the count."
With one out, David Ortiz had good fortune on his side, trying to pull back his swing but tapping an infield bleeder past the mound for a hit. Mike Napoli kept the rally going with a single.
Up stepped Sizemore, who belted an 0-1 slider from his former Indians teammate and easily cleared the wall in right.
"You face your friends all the time," Sabathia said. "Me and Grady are really close, and we have been for a long time. That's what makes it even more frustrating, giving up the home run to him. It just is what it is. You go out and compete against your friends and try to get the best of them. He got the best of me tonight."
The Red Sox no longer look at Sizemore as the feel-good comeback story. They look at him as a key ingredient in their lineup.
"To be completely honest with you, I'm not surprised one bit," Gomes said of Sizemore. "I'll tell you right now, if he's healthy, that's what you're going to see. If the tables were turned and he wasn't doing good, I would be completely surprised, to be completely honest. He's a heck of a player."
For Boston, the rally was the type they've lacked of late.
"Jonny leads off that sixth inning with a solo home run off of CC, who really kept us in check with a lot of offspeed pitches here tonight and then Grady gets the 0-1 breaking ball that he hits out of the ballpark and finally we've got a little bit of breathing room," said manager John Farrell.
And the bullpen took it home, despite the absence of closer Koji Uehara, who didn't pitch because of some right shoulder soreness he felt in pregame warm-ups.
Edward Mujica, who saved 37 games for the Cardinals last year, came on for the save, redeeming himself from a tough performance in the home opener. The righty fired a 1-2-3 ninth, ending the game with a punchout of Brett Gardner.
"I'm prepared for whatever situation," said Mujica. "Everybody in the bullpen is prepared for whatever situation. They gave me that opportunity today. I went over there and did my job."
For the third time in as many tries this season, Jon Lester produced a solid start. But this time he got a win to show for it.
The power lefty gave up six hits and two runs over 6 2/3 innings, walking two and striking out six. He threw 113 pitches, 71 of them for strikes.
"I felt all right," said Lester. "I had some grinds in there throughout the game. That's the Yankees. They're going to grind away at you and make you throw a bunch of pitches. Overall, none of that really matters. We won the game, at the end, that's all that matters."
Junichi Tazawa got four big outs, including a flyout to right by Derek Jeter that helped Lester out of a jam in the seventh.
"Well, when you think back to last October, we put him in some of the highest leverage situations with men on base and he excelled in it," said Farrell. "Tonight is no different. He was completely calm and confident."
Lester mowed the Yankees down early, with one exception. Alfonso Soriano led off the second with a towering homer to left to make it 1-0.
The Yankees threatened to come back in the seventh, as Ichiro Suzuki started a two-out rally with a single to right. Lester walked Brian Roberts. Kelly Johnson came to the plate 0-for-14 lifetime against Lester, but he ended that drought with an RBI single to right to make it a 4-2 game.
From there, the Red Sox snuffed out the drama, with the interim closer sealing the game.
"Koji is running a pretty historical career these past five years. It doesn't hurt to hand the ball off to a guy who had 30-plus saves last year," said Gomes. "We're in a good spot with a deep bullpen."