And as has been the case for much of the year, the Mariners had their chances to rally, but couldn't get the right hit at the right time.
For example, with the team down, 5-1, in the bottom of the eighth, the Mariners loaded the bases with nobody out and then watched as Franklin Gutierrez swung at a 2-0 pitch and popped the ball up foul off first base for an out, and Adam Moore hit into a routine 6-4-3 double play to end the threat.
"Again, I really believe that if we keep putting ourselves in those positions, somebody's going to come up with a big hit for us," Mariners interim manager Daren Brown said.
"And at that time of the ballgame, that's what we needed."
Vargas, who brought a 9-6 record and a 3.43 ERA into the opener of the three-game series and 10-game homestand, surrendered three consecutive hits to start the game, capped off by reigning AL MVP Joe Mauer's bloop RBI single.
Vargas threw 28 pitches in the opening inning, a struggle with efficiency that has been uncommon for the left-hander in this breakout season.
And even though Vargas fell behind, 2-0, by giving up another run in the second courtesy of a leadoff walk, a Jason Repko single, a passed ball by Moore and a Drew Butera sacrifice fly, he settled in and gave his team a chance to rally.
After Butera's sac fly, Vargas retired 11 of the next 12 batters and the Mariners responded with one run in the third, when Ichiro Suzuki tripled and scored on a Chone Figgins groundout.
But the Twins kept plugging away and broke the game open in the sixth, when Vargas gave up three hits in a row, including Danny Valencia's two-run triple. Two batters later, Alexi Casilla singled in Valencia to make it 5-1, and Vargas' night was done after six. He gave up five runs (four earned) on nine hits while striking out three and walking one.
"I felt good in the sixth," Vargas said. "I guess if I could just take one pitch back it would be the outside cutter to Valencia. It just kind of hung out there. We'd been throwing him in all night. ... I was trying to throw a back-door cutter. Hopefully he was going to give up on it or roll over it and hit a ground ball to [third baseman Jose Lopez] or [shortstop Josh Wilson]. It kind of stayed out there and rotated and didn't do anything, and he was able to hit it out there into the gap."
The Twins tacked on a run on a Mauer double off reliever Garrett Olson in the seventh, and the Mariners could only get one in the bottom of that inning on a Wilson single before Figgins ended the rally by grounding out with the bases loaded.
Figgins drove in Seattle's third run with a single in the bottom of the ninth, but Russell Branyan grounded out to end the game.
On the positive side of things, the Mariners saw the return to the mound of their closer, David Aardsma, who hadn't pitched since taking a line drive off the ribs in Baltimore on Aug. 18.
Aardsma worked a scoreless ninth, striking out the side while giving up one hit, and has allowed three runs in his last 15 appearances.
"He looked good," Brown said. "I thought his stuff was good, and that was good to see. He looks fine."
The same can be said for Vargas, who noted that he feels great even though he's pitched a career-high 158 innings and has taken losses in his last two outings -- one against the Yankees and Friday night's against the Twins.
"There hasn't been any change in the way I feel from the beginning [of the season] to now," he said. "I don't think that being fatigued or being late in the season has anything to do with the last couple starts.
"They're both good hitting teams, and [the Twins] were able to find some holes tonight and put some balls in the gap that ended up scoring those runs. It has nothing to do with where I'm at."