Third baseman Adam Kennedy's two-out error in the fifth inning allowed the Mariners to score three unearned runs on the way to a 4-2 victory that closed out a three-game sweep.
Without the error, which forced Anderson to throw a dozen more pitches in the inning, he might have been allowed to go deeper into the game.
Instead, he was stopped after five frames and 92 pitches, pinned with the loss despite allowing one earned run -- on a solo homer by Adrian Beltre in the second inning -- for the second consecutive start.
"It's tough," said Anderson, who gave up eight hits and walked one while striking out five. "Any time you feel like you're out of the inning, you relax a little bit. ... I made some bad pitches after that."
With runners at first base and second, Jose Lopez hit a hard ground ball that Kennedy tried to smother but bobbled, then was late in his attempt to hustle to the bag for a forceout at third.
That loaded the bases for former A's designated hitter Mike Sweeney, who drilled a two-run single to right, and Beltre followed with an RBI single to left.
"It was an in-between hop," Kennedy said, gamely standing at his locker in full-accountability mode. "I thought I could still get over there and get him."
Acquired in May to fill in for then-injured Mark Ellis at second base, Kennedy was moved to the hot corner when Ellis came off the 60-day disabled list on June 28. He's made 13 errors at third base, including six in his past 10 games.
"I've just been having a hard time with the depth [perception] on balls hit right at me," he explained. "You don't have that in the middle infield, where you can move to take the ball where you want it."
Kennedy has gone through long stretches of excellent defensive play, and his consistent bat has been a boon to Oakland's offensive resurgence; his batting average has hovered in the .280-.300 range all year, and he batted .351 in September.
But the errors -- including seven at second base, giving him a career-high 20 -- have come in bunches, and in a variety of ways: high throws, low throws, wide throws, bobbles and boots.
"If it was one particular thing," A's manager Bob Geren said, "maybe you'd be able to put your finger on it."
Asked if the recent spate of E's has crept into his head, Kennedy shook his head with a weary smile.
"I don't give a spit if I make 100 errors," he said. "I just don't like it when it affects the pitchers and their wins and losses."
This one did. It left Anderson with a record of 11-11.
"We made one mistake in the field and they capitalized on it, big-time," Geren said. "That was the difference."
Who knows? Without the error, maybe Jack Cust's leadoff homer to left-center field off Mariners closer David Aardsma in the ninth would have been a game-winner.
Instead, it was reduced to a footnote milestone. Cust reached the 25-homer mark for a third consecutive season.
"On a personal level, it feels good," Cust said. "I'd have liked to have a better year, but it's a nice accomplishment."
Beltre had opened the scoring by opening the second inning with a first-pitch blast to just right of center field, but Daric Barton followed Kurt Suzuki's leadoff triple in the fourth off righty Doug Fister with a game-tying double.
Fister, however, spent his night bending without breaking, and the A's never came up with the big hits that came so freely for them while putting together a 16-4 run before arriving in the Emerald City.
"This Oakland team came in swinging awfully effective," said Mariners manager Don Wakamatsu, whose club can claim a tie for second place in the American League West with a weekend sweep of the Rangers.
"They had some great games against Anaheim and Texas before this series, and I'm awfully proud of the pitching performances to negate that. [Brandon] Morrow yesterday, Felix [Hernandez] the first day and tonight with Fister."
Anderson, who went 4-0 with a 2.28 ERA in four September starts, provided the A's with some of their best pitching performances of the year.
He posted a 3.48 ERA in 14 starts after the All-Star break, lost only three times after July 24 and set an Oakland single-season strikeout record for rookies. He finished with 150 strikeouts over 175 1/3 innings.
"He's going to be one of the elite pitchers in the league, without a doubt," Geren said. "He's a special young man."
After noting his two-hit shutout at Fenway Park as the personal highlight of his first season and the double he gave up to Giants pitcher Matt Cain as one of the lowlights, Anderson said he was generally happy with his year as a whole.
"There's always going to be highs and lows, so you've just got to roll with it," he said. "But I'm pretty pleased. To get 11 wins and set a rookie strikeouts record, you can't be too unhappy with that."