Saunders, a veteran southpaw signed as a $6.75 million free agent to bolster the Mariners rotation, gave up four runs on seven hits -- including five doubles -- and walked four batters before exiting with a 4-2 deficit.
The new Seattle starter said he had trouble gripping the ball much of the night, something that affected reliever Charlie Furbush in a wild eighth inning as well.
"It was hard," said Saunders, who never seemed to get comfortable on the mound and asked for new baseballs several times. "It felt like the balls had some funny stuff on them. Not to make excuses, you have to make adjustments. But some of them were taking off.
"My arm felt good and I felt like my command was actually there, it was just tough to grip the ball. ... You saw Charlie go through it, too. I don't want to make excuses, but it was one of those weird things that happened tonight."
Veteran reliever Kameron Loe, who gave up two runs in three innings after replacing Saunders, agreed that the balls were "a little powdery, but I'm not going to blame that, that's for sure. I've seen it other places, but it's not like a common occurrence."
Manager Eric Wedge and catcher Jesus Montero acknowledged that both Furbush and Saunders mentioned the issue as well during the game.
Whatever the problem, it certainly didn't affect the A's pitchers, who held Seattle to two runs and five hits while recording their first win of the season.
The Mariners scored twice in the first on solo home runs off left-hander Tommy Milone with a leadoff bolt by Franklin Gutierrez and a two-out shot to center by Michael Morse.
It was Morse's third home run in two nights as he is off to a hot start in his return to the Mariners.
Morse hit three home runs in his first four seasons in Seattle back when he was a young player trying to find a spot in the Majors. But the 31-year-old outfielder has already equaled that power production in his first three games back with the Mariners this season after being acquired in an offseason trade from the Nationals.
Gutierrez's prodigious poke to left-center was the second leadoff homer of his career. But Milone, who won 13 games last year as a rookie, settled in after the shaky start and shut out the Mariners for the next six innings on just two more hits.
"Everybody knows he doesn't throw hard, but he can throw strikes," said Montero, who finished with two of Seattle's five hits. "He can hit spots. Early on Guti and Mike Morse hit homers and we were like, 'We've got this guy.' But he started to throw strikes and good pitches and he got us."
The Mariners seemed ready to add on in the second when Montero led off with a single and Jason Bay walked, but Milone got a double-play grounder from Robert Andino and struck out Brendan Ryan, starting a string in which he retired 17 of the last 18 batters he faced.
"That was a big double-play ball," said A's manager Bob Melvin. "That was kind of the turning point for him. It seemed like he found his release point a little more consistently after that.
"If there's anybody that can recover from a little bit of difficulty it's Tommy. He doesn't let too much get to him and just concentrates on where he's throwing that particular pitch and doesn't get too far ahead of himself."
Saunders never did find such a groove as he worked with runners on base throughout his short outing. The A's had runners on first and second with none out in the second, third and fourth innings.
Saunders did some damage control, limiting the A's to 2-for-10 with runners in scoring position in his four frames, and got some nice defensive help.
"He just didn't have the command with his secondary stuff that he typically does," Wedge said. "I thought he had a pretty good fastball and he came out and looked strong. He battled and controlled damage about as well as you can, considering everything.
"We saw the bulldog in him, the fact he'd bend, but not break. But he just wasn't ever able to really lock it in."
Saunders escaped the second on a perfect relay from Bay to Ryan to Montero that nailed A's rookie Nate Freiman at the plate as he tried to score on a two-bagger by Scott Sizemore.
Saunders also wiggled out of a no-outs, bases-loaded jam in the third by allowing just one run on a sacrifice fly by Yoenis Cespedes that tied the game at 2.
But Oakland's fifth double of the night -- a shot to right-center by Jed Lowrie -- plated two runs in the fourth and gave the A's a 4-2 lead. That spelled the end for Saunders, a 31-year-old veteran with a career record of 78-65 and an All-Star berth to his name in 2008.
Loe replaced Saunders and pitched two scoreless innings before giving up back-to-back homers to Lowrie and Chris Young leading off the seventh.