And with the game still tied in the 10th, Pedroia roped a single to right that put runners at the corners with one out. That set up David Ortiz for a sacrifice fly to right, which put the Red Sox ahead at last.
"Real nice," said manager Bobby Valentine. "That's what it was all about -- [Pedroia] solving the Vargas mystery with a home run to get us tied, and then a base hit in the 10th there, that was vintage. He took a 96-mph fastball and just laced it into right field. It's July 1, folks. Look out. New month. His month. I believe it."
Before the home run, Pedroia had just one hit in 15 at-bats in this series.
"Geez, I felt like it was 50 outfielders and a lot of infielders," Pedroia said. "I was hitting the ball good, just right to them, so it was frustrating. I just put a good swing on it and it felt good."
With the win, the Red Sox improved to 1-5 in extra-inning games this season and erased some of the sour taste of being fed walk-off losses twice in Seattle. Boston salvaged a split of the four-game series to remain 6 1/2 games behind the Yankees in the American League East.
The winning rally started when Ryan Kalish came off the bench with one out in the 10th and belted a double off the wall in center.
"Just stay aggressive, see a good pitch early, because a lot of times they're trying to get ahead," said Kalish. "They're not trying to walk you. They don't want to give up a run. If I get on, Pedey is right behind me. They're going to put something over the plate. I was just ready for it."
Pedroia's hit moved Kalish to third and gave Ortiz an RBI opportunity.
The lefty slugger, who is still looking for home run No. 400, hit it to deep right -- deep enough to bring in the run, though the milestone will have to wait at least another day.
"I [was] just looking for something over the plate," Ortiz said. "Those guys had been throwing everything off the plate to me."
The Sox again got a big performance out of the bullpen after starter Felix Doubront threw 103 pitches over just 4 1/3 innings. Doubront allowed three hits and five walks while striking out four. Somehow, Seattle scored just once against him.
After Doubront left, Matt Albers fired 1 2/3 innings, allowing a walk and no hits and then Scott Atchison was perfect for two innings, striking out one.
Vicente Padilla worked around a hit and a walk in the ninth to earn the win. Alfredo Aceves came on in the 10th to pin down his 19th save.
Of late, Doubront hasn't shown the same form as earlier in the season, when he was Boston's most consistent starter.
"I was feeling good and my arm was feeling good," Doubront said. "Just one moment, I lost my mechanics or the release point of the ball. You know, it was quick. I don't know what happened -- seriously."
Doubront was never in command in this one, but the Mariners mostly let him get away with it. In the third, Seattle at least got on the board. Chone Figgins led off with a single up the middle and stole second. Brendan Ryan's single to center put runners at the corners with nobody out. Ichiro Suzuki lifted a sacrifice fly to left and Seattle had a 1-0 lead.
The Red Sox, as they were for most of the series, were quiet offensively. But they got the hits they needed when it counted.
"You play four games here, guys get to thinking they're never going to hit one over the fence," Valentine said. "Their pitching today was very good. Vargas had a terrific changeup and their bullpen was coming right after us with good stuff. I'm glad we were able to score two runs and get out of here with a split."
And the fact that Pedroia had two big hits could be a very good sign going forward for the Red Sox.
"He's a good player," Vargas said of Pedroia. "He's shown that he can put his team back in the game when he needs to. I wouldn't take it back. It was a fastball away. For him to hook it out of this park, you tip your hat to him."
The home run was No. 6 on the season for Pedroia.
"I didn't even know I had [a drought]," Pedroia said. "That's good -- they're coming."