The slugger sent everyone to their heated cars and homes by belting a walk-off single to the warning track in right field with one out in the bottom of the 12th to beat the Rays, 3-2.
It was a stirring finish to a game the Red Sox trailed, 2-0, after eight innings and still were down a run with two outs and two strikes in the ninth before Xander Bogaerts came through with the equalizer, an RBI double off the Monster.
Ramirez also had a big hit in that ninth-inning rally, the RBI single up the middle that got Boston within one.
Three innings later, the Red Sox again had the man they wanted up at the plate. Ramirez, who delivered a two-run double in the 13th inning that beat the Marlins in Miami two days ago, stayed hot and again got the job done.
This one was for Boston.
"That's the only thing that kept me in the game and locked in, the fans, because it's cold out there, it was really cold," said Ramirez. "I think that a 'W' makes you feel better, all of us."
For the Red Sox, it was their sixth win in a row since a heartbreaking loss to the Rays on Opening Day. And for Tampa Bay, it was its sixth straight loss.
It was the first time the Red Sox have had a win of 11 innings or more in the home opener since the first game played at Fenway, when they beat the New York Highlanders, 7-6 in 11 innings on April 20, 1912.
Jackie Bradley Jr. started the winning rally with a leadoff double to right-center against Andrew Kittredge. Christian Vazquez pushed Bradley to third with a sacrifice bunt. Rays manager Kevin Cash then ordered an intentional walk to Mookie Betts, putting the game in Andrew Benintendi's hands.
Cash countered with lefty reliever Ryan Yarbrough, and Benintendi came back from an 0-2 count to walk.
Ramirez jumped on the first pitch he got from Yarbrough -- an 81-mph changeup -- and crushed it to the warning track in right, as the Red Sox roared out of the dugout to celebrate.
The man they pursued was Ramirez, who kept sprinting around to keep himself warm and avoid whatever cold liquid his teammates were trying to spray him with. He finally stopped for a group hug.
But the Red Sox came roaring back in the bottom of the ninth with that two-run rally against Rays closer Alex Colome.
David Price was magnificent for Boston, holding the Rays scoreless over seven innings for the second time in less than a week. In this one, the lefty walked three, struck out five and threw 91 pitches.
It was quite an opening for the grand old ballpark in Boston's Back Bay.
"That's Fenway. That's Boston," said Price. "It doesn't matter how many innings you go or what the weather is, the atmosphere is always going to be there. To get to play 81 home games, that's something you don't get to experience anywhere else."
MOMENTS THAT MATTERED Thrilling comeback, and a close call: The Red Sox thrilled their fans with a furious rally in the bottom of the ninth against Colome to come back from a 2-0 deficit. Ramirez belted an RBI single to make it a one-run deficit. An RBI double off the Green Monster by Bogaerts had the packed house on its feet. Bradley nearly won the game with a grounder toward the middle that second baseman Daniel Robertson ranged over to field. As Robertson threw across his body to first base, Bradley came close to beating the throw. But the call on the field by first-base umpire Alan Porter was that Bradley was out, and after a video review, the call stood, meaning there wasn't evidence conclusive enough to overturn it.
"It was big," said Price. "We had three hits heading into the bottom of the ninth and were able to put up four hits in that ninth inning off Colome, who has been extremely tough against us and the rest of the league. That was huge. We've done that a couple times this year. That's what good teams do."
Rookie lefty on point: In the 12th, the Rays had the go-ahead run at second with one out. But Poyner didn't buckle, getting Duffy on a lineout to right and striking out Kevin Kiermaier.
"He's got the confidence from us and the coaching staff and everybody," said Ramirez. "That's all you need from everybody is confidence. Go out there and do your job."
QUOTABLE "I saw him early in December and we talked about it, and he said, 'You don't have to worry about me, I'll be fine, I'm healthy.' He's hitting third for a reason. I do believe in him. I know the quality of his at-bats, I've seen him throughout his career and we challenged him, and he's doing a good job." -- Red Sox manager Alex Cora, on Ramirez
SOUND SMART WITH YOUR FRIENDS This was the eighth time the Red Sox have had a walk-off win in the home opener, and first since Mo Vaughn's grand slam on April 10, 1998.
FIVE STARS FOR MOOKIE When Tampa Bay's Adeiny Hechavarria hit a blooper into short right field with two outs in the top of the second, it looked like the classic case of a ball that would fall into no-man's land. But Betts had other ideas. With Ramirez and second baseman Eduardo Nunez also in pursuit, Betts sprinted in for a five-star catch, according to Statcast™.
Betts had a 14-percent catch probability, but he didn't even need to leave his feet for the fine grab. Betts had a sprint speed of 29 ft/second (30 is considered elite) and a near flawless route in which he covered 91 feet in 4.6 seconds. More >
WHAT'S NEXT Rick Porcello, who is coming off a strong season debut (5 1/3 innings, 1 ER), faces the same team again (the Rays) in his first Fenway start of 2018 on Saturday. Porcello makes this start on six days of rest due to several team off-days.