But in a duel of designated hitters, David Ortiz answered, hitting a two-run shot into virtually the same spot with one out in the eighth to win the game. The Red Sox defeated the Yankees, 4-2, in the first meeting of 19 this season between the two storied rivals.
Ortiz is in his final Major League season and A-Rod has only one more to go after this one.
"Things are coming along for me nicely," A-Rod said afterward. "But if you told me 10 years ago that me and Big Papi would be hitting home runs at 40 I probably would have laughed."
Rodriguez crept closer to becoming the fourth player in Major League history to reach the coveted 700-homer mark. He's now nine away at 691. He's hit 58 of those homers against the Red Sox and 28 of them at Fenway Park.
Ortiz has simply crushed the Yankees over the course of his 20-year career. The homer on Friday night was his 48th against New York and he still has an entire season left to add to that number.
"I've been seeing him do that since I was in [Class] A ball in Appleton, Wisc., for the Mariners," A-Rod said. "He's unbelievable. I don't have anything else to say. He's just unbelievable."
It is a long season, and for A-Rod, it had been a long month of April. But with four hits in his last two games, he's finishing it off with a flourish. Manager Joe Girardi rested him for two games at Texas earlier this week after A-Rod felt a twinge in his left oblique warming up to hit against the Rays in the sixth inning Sunday at Yankee Stadium.
MRIs on the afflicted area were negative. Both A-Rod and his manager breathed a big sigh of relief.
"It was smart what Joe did," Rodriguez said. "When I was swinging in the cage on Sunday something didn't feel just right. So he didn't want to take any chances and got me right out of there. Then he gave me the extra game off, which was also a smart thing to do. If the oblique pops, it's a dangerous injury. You can be gone for a long time."
To that point, Giants right fielder Hunter Pence missed the final six weeks of the 2015 season with an oblique injury of the same nature that just wouldn't go away. And in fact, Girardi was nervous the day he had to pinch-hit for the right-handed-hitting A-Rod.
"Anytime anyone leaves with an oblique you're not really optimistic because they take awhile, depending on the severity of it," Girardi said. "Sometimes even when players physically feel ready I don't think they have the strength they had before. It takes some time to get that back."
Rodriguez has this year and next to go on his contract and some significant milestones to shoot for. Aside from becoming only the second right-handed hitter to reach the 700 homer plateau, fellow Yankees slugger Babe Ruth is in third place on the all-time list at 714, just 23 away.
A-Rod will be 41 on July 27. He hit 33 homers last season, and both of those marks are certainly within reach this year. But A-Rod said that even 700 right now is a mirage.
"To me, it's still a long, long way away," he said.
A-Rod was batting .100 and on an 0-for-19 streak, which he snapped with a homer against the Mariners at home on April 17. Since then, he's been on steady progression back, lifting his batting average almost 100 points to .194 after the game on Friday night, when he also could have had a ninth-inning single save for a great diving play by shortstop Xander Bogaerts.