CHICAGO -- Ron Gardenhire had the perfect remedy for a depleted bullpen -- Johan Santana.
Jim Thome hit his 498th career home run, a solo shot off reliever Juan Rincon in the eighth inning. It's the third consecutive game Thome has homered, giving him 26 on the season.
Santana (15-11), who had given up eight runs in 12 innings in losing his last two starts, yielded only one run on four hits. He walked two while throwing 116 pitches to help the Twins snap a season-high six game losing streak.
Gardenhire watched the Minnesota bullpen blow a six-run lead in the ninth on Friday and a two-run lead on Saturday.
"He might have gone out there for 130 (pitches) if I had my way today. I've been pointing out to that bullpen and it ain't been working out too good lately," Gardenhire said. "They're a little worn down and I was ready to just keep on going (with Santana)."
Santana escaped trouble in the sixth inning, getting Paul Konerko to pop out with the bases loaded with two outs.
"I feel good. Sometimes things don't work out the way they should or the way you want," Santana said. "Especially in a game like today where we had been losing so many games, that's when you want to end everything. I'm very happy that we got this win."
After blowing his last two chances, Joe Nathan pitched a scoreless ninth for his 30th save in 34 opportunities.
Jon Garland (9-11) gave up five runs in eight innings, but only one of them was earned because of two fielding errors by Alex Cintron. The White Sox have lost 20 of their last 27 games and are guaranteed their first losing season since 1999.
Garland fell to 1-4 over his last seven starts. He allowed five hits, striking out five and walking two.
"It's definitely a part of the game," Garland said of the errors. "It's just a matter of overcoming them and today I didn't do that."
Cintron's first error came in the third inning, when Garland gave up a two-out walk to Nick Punto and Jason Bartlett hit a ball that the third baseman couldn't handle. Kubel followed with an RBI single to tie it a 1-1.
The second error came in the fifth, when Luis Rodriguez hit a two-out single and Cintron again booted Bartlett's ball. Kubel followed by hitting a 2-1 pitch from Garland into the stands in right-center to give the Twins a 4-1 lead.
"I went out there to give the team a chance to win and I threw the ball well," Garland said. "It's a hard game -- things don't always go your way. Hopefully the day you're out there they do, but you have to get back on the mound and keep pushing."
Justin Morneau added an insurance run with an RBI triple off Garland in the eighth.
The White Sox scored against Santana in the second inning when Jermaine Dye doubled and scored on Cintron's RBI single.
Twins catcher Joe Mauer started his first game since Aug. 25 and was 1-for-3 after being out with a left hamstring injury.
"He's 75 percent, as they say. He didn't run much. He put a good swing on the ball and did a good job behind the plate," Gardenhire said. "You can just see the difference, the way the game goes along."
Dye had three hits. ... Before the game, the Twins purchased the contract of C Matthew LeCroy from Triple-A Rochester. To make room for LeCroy, the Twins placed C Jose Morales on the 60-day disabled list with a sprained left ankle. ... Santana has reached double-digits in strikeouts six times this season.