Oakland catcher George Kottaras delivered the big blow, a three-run home run in the fourth, just the fourth long ball Hernandez has allowed in his past 17 starts.
Hernandez had gone 9-1 with a 1.62 ERA in 15 outings since June 17, with five shutouts and a perfect game dotting one of the most dominant stretches in Mariners history. He was 4-0 with a 1.08 ERA and three shutouts, including the perfecto, while earning AL Pitcher of the Month honors in August.
But September has now brought back-to-back losses to the AL West-rival Angels and A's, with Hernandez posting a 6.23 ERA with nine earned runs and 20 hits in 13 innings, a far cry from the dominance he'd displayed while racking up nine wins over a 10-week stretch.
The 26-year-old has already thrown a Major League-high 209 innings, but manager Eric Wedge said he doesn't think Hernandez is fatigued.
"He's done a great job of taking care of himself physically and worked so hard between starts. He's still strong," Wedge said. "He was just up a little bit today, just a little off. When they got to him, usually the pitch was up and over the plate. Felix has been so good for so long, he was just a little off today."
Hernandez needed 96 pitches to get through 4 2/3 innings, his second-shortest start of the season (he went 3 2/3 innings in a 9-3 loss on May 16 at Cleveland). The 11 hits he allowed tied a season-high Hernandez set May 11 at the Yankees and the five earned runs were the most since a 5-4 loss to the Padres on June 12.
The A's got to Hernandez for an unearned run in the first when right fielder Eric Thames misplayed a single by Yoenis Cespedes, with the ball spinning past him as Seth Smith scored from first.
Seattle tied it back up in the second when Michael Saunders singled, moved to second on a four-pitch walk by Luis Jimenez and scored on Brendan Ryan's base hit to right.
But the A's, in the thick of the AL Wild Card race at 77-60, jumped on Hernandez for three runs on Kottaras' home run in the fourth for a 4-1 lead.
"I've often said that those type of homers feel like they put more runs on the board than they actually do," said A's skipper Bob Melvin. "To get to 4-1 against Felix feels like it's a 10-run homer."
Oakland then knocked Hernandez out in the fifth with two runs on four straight hits even after Thames threw out Cespedes trying to go from first to third on a single to right by Brandon Moss.
"It's frustrating when you've got nothing going on. That's what happened tonight," Hernandez said. "It happens. I just have to get ready for the next one and look forward. I was trying everything out there and nothing worked. I was opening up too much, I fell behind, left pitches up. That's why I gave up six runs."
The Mariners did little to counter against rookie right-hander A.J. Griffin, who improved to 5-0 with 5 1/3 innings of one-run ball with six hits and seven strikeouts.
Jimenez, a September callup making his first Major League start at age 30, walked in the second inning and then got his first hit -- a single up the middle -- in the fourth. He finished 1-for-3 with the walk and a memory that will last a lifetime.
"This was the day I really wanted to do it because my parents were here [from Venezuela] and it was my first start," said the 6-foot-3, 280-pound designated hitter. "I just wanted to show I could do something. Getting my first hit, that a very good feeling. I'm very proud of that."
Erasmo Ramirez and Hector Noesi made their first appearances in relief since being recalled as well. Ramirez had a scoreless seventh, with one hit batter, while Noesi finished up the final two innings with one hit and a walk.
Both young right-handers will get a chance to start several games in the final three weeks, so this was a chance to keep them tuned up.
"I wanted Ramirez to throw one inning because he's going to start earlier than Noesi," Wedge said. "And Noesi pitched later in the season in Triple-A, but this is his day to throw so I wanted to see him go a couple innings. And I'm glad we did because he was a little shaky his first inning, but much better his second."
The loss dropped the Mariners to 67-72, though they've still won 18 of their past 23 at Safeco.