Delmon Young added two hits and two RBI, including a run-scoring triple in Minnesota's three-run first.
Felix Hernandez (7-8) pitched seven innings for the Mariners, yielding three runs and seven hits.
"We got to him early, but fortunate enough, that was all we needed," Young said. "You just have to get a ball that you can barrel up and just pray it's before two strikes because it's not fun up there with two strikes against him."
Mauer batted .344 in July despite being bothered by tendinitis since he took a foul tip off his right shoulder earlier in the month. The reigning American League MVP got a cortisone shot after the game and likely will rest for the next two days.
Seattle has lost six straight and its 6-22 record for July matched the franchise record for losses in a month, set by the 1977 expansion team in August.
"I'm not going to sit here and make excuses," manager Don Wakamatsu said. "We have to play better. Offensively, to go out there and watch three or less runs, it puts a strain on the pitching staff. We've had a lot of moves, had some injuries, but with that kind of offense, little things get magnified and cost you ballgames."
Seattle has scored two or fewer runs in 49 of its 105 games.
Slowey (10-5) allowed three hits, tying a season low, and struck out five. The right-hander has allowed just one run over 14 innings covering his last two starts, both victories.
As the Twins struggled midway through July, poor starts by Slowey and Nick Blackburn led to rotation questions. With Brian Duensing -- a former starter in the minors -- pitching well in relief, Slowey or Blackburn were on the verge of moving to the bullpen.
"They're not going to say anything short of encouragement until the very end, until they want to make a change," Slowey said.
Blackburn's struggles eventually cost him his starting spot and Slowey has responded with back-to-back strong efforts. He pitched six innings in Minnesota's 10-4 win at Baltimore in his previous start.
"I think maybe I'm executing a little better earlier in counts, giving myself an opportunity to be up 0-1, 1-2 rather than 1-0, 2-1," Slowey said. "I think that is certainly helping. Other than that, there's really never any lack of preparation in our clubhouse. Occasionally, there's lack of execution and I think the last couple of starts I've executed better."
The Twins jumped all over Hernandez, who was third in the American League with a 2.86 ERA and second with 145 strikeouts entering the game.
After Denard Span flew out on the first pitch, Alexi Casilla tripled to left field and scored on Mauer's single. Young followed with a triple to right, making it 2-0 after just eight Hernandez pitches.
Jim Thome watched the first two balls from Hernandez before eventually belting an RBI double to left against an outfield shift.
"They came out swinging, first pitch," Hernandez said. "I threw a couple of good pitches and they hit it. It was like, 'Geez.' They scored three runs. I've got to stop them right there."
Swinging early and often worked for the Twins as they stayed away from getting behind in the count against Hernandez. Opponents are hitting just .118 with two strikes against the Seattle ace, the second-best mark by an AL starter this season.
"Sometimes when you know guys are going to pound the zone like him, Cliff Lee, sometimes you have to get them before they get you," Span said. "You know once you get down in the count, they're probably going to put you away."
Slowey retired 12 straight hitters following Casey Kotchman's single in the first inning. He faced just two over the minimum and tied his longest appearance of the season.
Jose Mijares finished the four-hitter.Notes
- Thome's first-inning double gave him 1,599 RBI, moving him into a tie with Nap Lajoie for 31st on the career list. Goose Goslin is next with 1,609 RBI.
- 1B Michael Cuddyer extended his career-high hitting streak to 15 games with a single in the sixth inning. Cuddyer's infield bouncer was fielded by Hernandez, whose throw was wide of first base and it was ruled a hit.
- Mauer is hitting .519 (14 for 27) with two homers in his career against Hernandez.
- With 3B Matt Tuiasosopo inserted into the lineup after being recalled from Triple-A Tacoma earlier in the day, the Mariners have used 26 different lineups in their past 26 games.
- Mariners star Ichiro Suzuki struck out three times and lost a string of 10 straight months with a .300 average. He finished July with a .246 average, marking the first time since September 2008 he has not hit at least .300 in a full calendar month.