"It's very frustrating," Villanueva said. "I thought today I had the best fastball command I've had maybe since I started. The problem, the only problem, was my slider to lefties, the backdoor slider, I just couldn't get it down and in enough.
"I had a few of them, especially early in the game, too. Two strikes, that's my bread and butter to lefties. I was pulling off a little bit, and it spun in there."
Villanueva entered play with a 4-0 mark and 2.54 ERA in five starts, but he allowed more than three earned runs for the first time this year.
For a while it looked like Villanueva's streak would continue, as he carried a 3-1 lead into the fifth inning, but Thames capitalized on one of those wayward sliders.
It's a moment that Thames won't soon forget.
"It's different when you're playing behind somebody and then face them," said Thames, who went 1-for-3. "I knew his offspeed is plus-plus and he likes to locate. Guys like that are tough in general, so I looked at video, I talked to (Michael) Saunders and some of the other guys and we collaborated on approaches and it worked out for us tonight."
Villanueva's struggles carried over into the sixth as well. He surrendered a one-out double to Saunders, and two batters later, John Jaso hit an RBI single to right field. That gave the Mariners a 4-3 lead and put Villanueva on the hook for his first loss.
The 28-year-old allowed seven hits while striking out six and not walking a batter. Despite the hanging slider to Thames, it was still another strong outing by Villanueva who has become the club's most reliable starter following injuries to Brandon Morrow, Drew Hutchison and Kyle Drabek.
The Blue Jays are constantly monitoring Villanueva's health because of what he went through in 2011. The veteran right-hander had to be shut down after 13 starts because of a right forearm injury, and it's something the club is looking to avoid this time around.
That's one of the main reasons why Villanueva was pulled after 84 pitches on Wednesday night but he said health hasn't been an issue this year.
"Physically it's a world of difference," Villanueva said when comparing the two seasons. "I feel healthy. Last year I would have said I feel tired, but it wasn't really tired, it was just hurt. The day I pitched I felt OK because we did a bevy of things in the training room to get me ready, but the four days after that were just a living hell for me.
"I just couldn't take it anymore. But this year, my body, I feel great, still. I felt very good today again and I've been recovering well."
Toronto's bats struggled for a fourth consecutive game. On Saturday, the club had the Major League's top-ranked offense, but since then has scored seven runs.
The bats did get off to a relatively hot start against Mariners right-hander Blake Beavan. Colby Rasmus sent the first pitch he saw in the first inning over the wall in right-center field. He is just one away from the 20-homer plateau, something he has done just once in his four-year career.
The Blue Jays' offense continued to produce in the fourth, as Kelly Johnson hit his 12th homer of the year with a solo shot to center field. Toronto would add one more run in the fifth on a sacrifice fly by Jeff Mathis but was shut down the rest of the way. Beavan allowed seven hits over 7 2/3 innings while striking out four en route to his seventh victory.
The loss meant the Blue Jays were swept by Seattle in a three-game series for the first time since June 29-July 1, 2007. They've lost four consecutive games and will look to put an end to that skid when the club travels to Oakland for the start of a four-game set against the A's on Thursday night.
"They're hot, which means they're probably due to stumble a little bit," Johnson said of the A's. "After playing like that, I think we're going to be ready to get going.
"Obviously we need to get the bats going. We need to score some runs, manufacture, do things with Jose (Bautista) out the lineup. It'll turn, it'll be all right."