What happened was the Boston slugger drove in both runs, including the go-ahead score in the sixth inning with a tape-measure homer, while Bronson Arroyo held Oakland in check over seven strong innings, helping to keep the Red Sox 1 1/2 games ahead of the Yankees in the American League East.
The Sox have won a remarkable 14 straight one-run games at home. Their last such loss was a 4-3 setback to the Blue Jays on April 19.
With the game tied at 1, Ramirez belted the first pitch he saw from Dan Haren (13-11) over the Green Monster with one out in the sixth for his 36th homer.
"I don't have the best view, but it looked like his upper half opened up," Red Sox skipper Terry Francona said. "He gets the barrel to it, and knocks the heck out of it. Sometimes he has the ability to almost sense what's coming, get a pitch and not hit a single. It's amazing how he can do that."
"It was a split that kind of ran in," Haren said. "I'd done a pretty good job of keeping it down the whole night, but that was nowhere close to being a strike. But, still, it's not where I want it to be, and I'm just pretty frustrated looking back on it because I had kept it down so well the whole game.
"And I was kind of determined not to make any mistakes, and for the most part, I kept the ball down pretty well -- and that pitch just got away from me."
Ramirez hadn't homered at Fenway since Aug. 10.
"I think Manny wants to be the man," Johnny Damon said. "He takes it personally when they walk Ortiz, and he wants to get the job done. I wouldn't put it past him to hit .300 by the time the season is over. We know that when Manny gets locked in, he really gets locked in."
Ramirez now has 426 homers, tying him with Billy Williams for 36th on the all-time list.
"I told you guys, that crazy [guy], when he wants to hit, he hits," Ortiz added. "Manny's going to hit when we need him. Manny's a great hitter. Manny's a box full of surprises. When you think you have the guy, the guy comes out and 'boom.' Manny is fine."
Before Ramirez's sixth-inning moon shot, the story of the game was Red Sox starter Bronson Arroyo.
He was perfect through four innings, retiring the first 12 batters before walking Scott Hatteberg and Jay Payton to lead off the fifth.
"He takes it personally when they walk Ortiz, and he wants to get the job done. ... We know that when Manny gets locked in, he really gets locked in."
-- Johnny Damon, on Manny Ramirez
"I think we mixed pitches pretty well tonight," Arroyo said. "First inning, I got them out on a couple of changeups. I don't know, maybe I started thinking a little bit or something, but I felt strong today and I was locating my fastball better than I have in a while."
The right-hander appeared to be on the edge of getting out of the inning before Marco Scutaro lined Oakland's first hit to left, scoring Hatteberg and tying the game, 1-1.
Arroyo (13-9) finished his night after 111 pitches, allowing three hits and one run.
"I thought his stuff was very crisp," Francona said. "He didn't give up very many hits. In the one inning, he has the walks. I don't just think it was loss of command. He had two 3-2 counts, and Payton has a real good at-bat. We turned two big double plays."
After quickly getting two outs in the eighth, Jonathan Papelbon allowed a two-out double to Jason Kendall, who advanced to third when Edgar Renteria made his 28th error fielding a relay from Trot Nixon. But Papelbon, a 24-year-old rookie, found his focus and got Mark Kotsay to fly to Ramirez in left to end the threat.
Mike Timlin pitched a perfect ninth for his ninth save in 15 chances.