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In a game that pitted the pitchers with the two lowest earned-run averages in the history of Safeco Field, balls flew out of the ballpark at a surprising rate.

But in the end, four homers by the A’s trumped one by the Mariners, and Oakland handed the Mariners a 6-3 loss that dropped them a season-high 11 games under .500.

On the heels of Thursday’s heartbreaking loss in Anaheim, the Mariners watched the A’s score all their runs via homers — two by a rapidly rising nemesis, Yoenis Cespedes. Cespedes’ second blast, off still-struggling reliever Tom Wilhelmsen in the ninth, stretched a one-run Oakland lead to three.

Cespedes had been limited to designated-hitting duties for the past week because of hamstring tightness, but returned to left field for this one.

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“Evidently, he likes to play the outfield,’’ Oakland manager Bob Melvin said. “You could see his whole demeanor today — he was just in a better mood. Batting practice, hitting fungoes, and taking ground balls at short. He likes playing the full game.”

Mariners starter Hisashi Iwakuma came into the game with the lowest ERA (1.88) of any pitcher with at least 60 innings at Safeco, followed closely by Bartolo Colon (1.91), who happened to be Oakland’s starter.

But Iwakuma, who lost for the first time this year at home, ran into immediate trouble.

Facing Cespedes, Iwakuma gave up a massive two-run homer to left. It was Cespedes’ ninth homer against the Mariners in 30 career games (with one still to come), and ended Iwakuma’s streak of 21 consecutive innings at Safeco without allowing an earned run.

But the longball became the Mariners’ friend in the third off Colon, who came in with the best record (10-1) of any visiting pitcher at Safeco with at least seven decisions. Following one-out singles by Brendan Ryan and Endy Chavez, rookie Nick Franklin launched a blast into the right-field bleachers for a three-run homer.

“I was looking for something to hit to the outfield, and luckily he left a changeup up,’’ Franklin said of his first career homer at Safeco. “I tried to square it up as best I could.’’

Colon had struck out Franklin on three pitches in the first inning, making him look bad in the process.

“He plain beat me,’’ Franklin said. “I don’t think I was ready for it. The next at-bat, I wasn’t going to let anything get by me.”

That kind of attitude and execution has made Franklin one of the few Mariner bright spots these days.

“He’s been doing great,’’ Mariners manager Eric Wedge said. “He’s up there ready to hunt the baseball, but takes the walks when they don’t come to him. He’s playing aggressively at second base. He’s playing with no fear. I love that.”

Iwakuma didn’t hold that lead long, however. Not even for one batter, in fact, as Jed Lowrie led off the fourth with a homer to center. It was the first time in 25 career appearances at Safeco — 18 starts — that Iwakuma had allowed a multi-homer game.

“Some of the pitches were up in the zone, and they took advantage of that,’’ Iwakuma said through interpreter Antony Suzuki. “Overall, I felt pretty good on the mound. The pitches were there. It’s just that the homers I gave up were not where I wanted location-wise, and they cost me.”

But the A’s weren’t finished. Leading off the sixth, Crisp reached the seats in right field to give Oakland the lead to stay. Iwakuma suffered his second straight defeat as his ERA rose from 2.06, second-lowest in the American League, to 2.26.

“He’s been up a little bit more,’’ Wedge said. “The homers tonight were all splitties (split-fingered fastballs) he left up and over, and they put good swings on them. I’ve talked about the quality of his misses a lot this year. He’s just been a tad off on that.

“He battled through good tonight, gave us a chance to win the ballgame. He just wasn’t quite as sharp with some of his secondary stuff.”

The Mariners didn’t help themselves on the basepaths. Kyle Seager led off the sixth with a single, but was thrown out at third trying to advance two bases on a passed ball by Oakland catcher Derek Norris. Kendrys Morales and Raul Ibanez followed with singles, but Colon worked out of it.

“Once he slowed down and kind of stuttered around second base, you’ve got to shut her down,’’ Wedge said. “If he just keeps going, maybe it’s a different story.”

In the seventh, Michael Saunders led off with a beautiful bunt single but was promptly picked off first base by Colon.

“Michael’s trying to steal a bag right there,’’ Wedge said. “He just broke a tad early. That’s probably a fraction of a second from being dead-on where he steals that bag, very similar to what Brendan Ryan did earlier in the game.”

Colon, 10-2 this season, limited the Mariners to seven hits over eight innings. Grant Balfour worked the ninth for his 18th save in 18 attempts.

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