Seattle's defense committed a season-high four errors on the night as the Mariners fell to 52-61 on the season.
"It happens," said Hernandez. "It's baseball. Errors are part of the game. We just happened to make a couple mistakes and fell behind a lot. They capitalized and scored some runs."
The King wasn't at his best either, giving up nine hits and three walks with three strikeouts before giving way after 101 pitches. Hernandez saw his record drop to 11-5 with his first loss since May 25 against the Rangers. His ERA stands at 2.39, still the best in the American League.
"He wasn't getting a whole lot off the corners," said Mariners acting manager Robby Thompson. "It seemed like it was a pretty tight strike zone. And then when he did miss, he was out and over the plate and he got hit. Even with the sloppy defense, we've seen a sharper Felix, obviously. But hey, we're all human and he still pitched a pretty good ballgame."
But this night swung Toronto's way from the beginning, as Blue Jays shortstop Jose Reyes greeted Hernandez with a leadoff home run, driving a first-pitch fastball over the wall in right center. It was just the second leadoff home run allowed by Hernandez in his career, the other by Ian Kinsler of the Rangers in 2011.
Hernandez has given up just 12 home runs in 24 starts, and he had allowed none in his previous five outings.
"He's one of the best pitchers in the game," said Reyes. "I went up looking for a fastball right in the middle the first pitch and I tried to put my best swing on the ball and that's what happened."
Not all the Blue Jays were as impressed.
"We battled him good. We put some good at-bats on him, worked into counts, and he didn't get some calls he probably normally gets," said center fielder Colby Rasmus, who had two singles and a walk against Hernandez. "To me, he's just another pitcher. Ain't nothing special to me. Up here, all the pitchers are good."
The Mariners' defense let Hernandez down in the fourth inning with errors by Kyle Seager and Brad Miller leading to a trio of unearned runs when Emilio Bonifacio delivered a two-out, two-run double and Reyes followed with a run-scoring single to make it 4-0.
Seager had two errors on the night and Miller also dropped a ball on a stolen-base attempt midway through the fourth-inning rally, a miscue that kept Hernandez from getting out of that mess.
The Blue Jays kept pounding away in the fifth, with three straight two-out singles tacking on two more runs and a six-run lead. Hernandez's 4.65 ERA against the Blue Jays in 12 career starts is his highest ERA against any AL opponent
Meanwhile, the Mariners made no progress against Toronto right-hander Josh Johnson, who came in at 1-8 with a 6.60 ERA and left after allowing just five hits in five scoreless innings.
Rasmus went above the center-field fence in the sixth to rob Kendrys Morales of a home run. On the flip side, Mariners left fielder Raul Ibanez fielded a double in the seventh inning and spiked his throw into the grass about 30 feet in front of him as Toronto added another run.
Even the Safeco crowd had a decidedly pro-Blue Jays feel for a second straight night, as a large percentage of the 28,198 in attendance were wearing Toronto colors and cheering for the visitors.
"Unbelievable, huh?" said Hernandez. "That's crazy. I don't know. Probably because we're close to Vancouver, that's why. But it's crazy."
Seattle finally crossed the plate with a two-run triple by Miller in the seventh off reliever Juan Perez. It was Miller's fourth triple in 34 games.
Miller helped overcome his sixth error of the season with a 2-for-4 night at the plate, but fellow rookie Nick Franklin was 0-for-3 with a walk as his hitless streak reached 27 at-bats.
"It's kind of youth showing a little bit right now," said Thompson. "But the experience he and Franklin are getting, offensively and defensively, they're only going to get better for it."
Carter Capps, recalled from Triple-A Tacoma earlier in the day, pitched two innings and allowed two hits and one unearned run.
The victory clinched the Blue Jays' first series win at Safeco Field since 2004, as they improved to 53-60 going into Wednesday afternoon's finale.