"For the most part, I was missing location-wise, catching too much of the fat part of the plate, and that was the main issue today," Iwakuma said through translator Antony Suzuki.
The Red Sox slugged five homers, including a go-ahead solo shot by rookie center fielder Jackie Bradley Jr. off losing pitcher Blake Beavan in the fifth, as they improved their American League-best record to 55-37.
Seattle came into the game having won five of its last seven, but it fell to 40-50 with the loss and burned through five relievers in the process.
Iwakuma has given up 10 home runs in his last four starts after allowing just 10 in his first 15 games of the season. The 32-year-old took a no-decision in his abbreviated effort and is now 0-3 with a 6.83 ERA in his last five starts after opening the season 7-1 with a 1.79 ERA.
"The home run has really hurt him the last four or five starts," said manager Eric Wedge. "He's just missing up and over the plate. We had a lot of that going on tonight, both sides did. But tonight I thought he was a little flat, too. He just didn't have the same edge on his pitches that we've seen.
"There's no reason for him to be fatigued. We're halfway through the season. He's a guy we normally keep below 100 pitches and he's had some extra days. He's strong with the way he's worked, so he just has to get back on line."
The former Japanese standout is still 7-4 with a 2.97 ERA with one start remaining Sunday against the Angels before the Midsummer Classic break, but he no longer leads the AL in ERA. That honor now belongs to teammate Felix Hernandez at 2.69, while Iwakuma dropped all the way to seventh.
Boston tacked on eight more hits and five runs off five Mariners relievers, with Beavan taking the loss after lacking his normal control in issuing a walk and hitting a batter while also allowing a pair of hits and the eventual game-winning home run.
Beavan hadn't pitched in the last eight days, but Wedge wasn't using that as an excuse for the long reliever.
"That's his role. It is what it is," Wedge said. "He still has to go out and execute pitches. We've had him in that role before and he's had days off and gone out and given us four to five innings and given us a chance. But today we just couldn't get anybody out. Guys struggled in the bullpen. It was one of those days.
"They did, too, but when they went to their middle-innings guys, they did a nice job and get them deep into the ballgame, and that was the difference."
Designated hitter Kendrys Morales hit a pair of home runs to give him 13 for the season and rookie shortstop Brad Miller delivered a three-run double in the second as the Mariners' offense continued its recent surge.
Going back to the fourth inning of Monday's 11-4 win, the Mariners scored in a franchise-record eight straight innings before stranding runners at first and third in the fourth and then failing to cross the plate until Miller forced in a run in the eighth with a groundout.
Morales was 3-for-5 with three RBIs, raising his average to .280. Miller went 3-for-5 with two doubles and four RBIs from his leadoff spot, continuing his instant impact in just his 11th Major League game.
"It was a real good night for Kendrys," Wedge said. "It feels like he's starting to heat up a little bit. There were a lot of encouraging things offensively for us right now, with the younger guys as well as some of the veterans. That's the positive you take out of it."
But in the end, this was the kind of game where Miller was kicking himself for settling for a double on his second-inning at-bat, the way things played out.
"There was a lot of back and forth and a lot of good swings. There was a lot going on," Miller said. "We were able to get some runs early and I still wish I'd tried to get to third for Nick [Franklin] there with one out, maybe add some more. We did a good job, but they shut us down from there."
Raul Ibanez saw his 13-game hitting streak snapped with an 0-for-5 night, though Kyle Seager extended his string to nine straight games with a 2-for-5 outing that raised his team-leading average to .288.
Red Sox rookie Allen Webster lasted just 2 1/3 innings in his sixth Major League start, giving up seven runs on six hits, including both of Morales' homers. But Boston's offense took the 23-year-old off the hook as David Ortiz led the onslaught with a 4-for-5 day with a home run and two doubles, tying Harold Baines' all-time record for career hits by a designated hitter at 1,688 in the process.
"He's a great hitter," said Wedge. "He's been driving the ball, using the entire field, extra-base hits as well as singles. He's a tough one to pitch to."