It was a rough outing for Blackburn, who gave up back-to-back homers to Adam Dunn and Alex Rios in the fifth and surrendered six runs on nine hits over five frames.
"I can't begin to explain how frustrated I am right now," said Blackburn, who fell to 4-5 with a 7.74 ERA. "It's like I'm not getting very many breaks. Guys go through streaks like that, but it's not fun. I guarantee you that. I'm not enjoying myself right now."
Blackburn was faring OK through his first four innings -- he had allowed two runs on five hits -- but ran into trouble in the fifth. Alejandro De Aza singled with one out before Kevin Youkilis added a two-out single to center field.
The sinkerballer was just one out away from getting out of the jam, but Dunn crushed a 1-1 sinker to the opposite field for his 24th homer to give the White Sox a 5-0 lead. And two pitches later, Rios homered on an 0-1 changeup to give him his second homer in as many days.
It's been a tough year for Blackburn, who has just one quality start in 11 outings, with 13 homers allowed. But Twins manager Ron Gardenhire said he's sticking with Blackburn in the rotation despite his struggles.
"This was a bad start for him today, but he's battled better," Gardenhire said. "We like what we've seen, but today was not one of them. There are not many options. Some of these guys have to get people out."
Minnesota didn't get on the board against Sale until the fifth, when Brian Dozier connected on his third homer of the year and his first since May 16.
But the White Sox put the game out of reach in the sixth, scoring three runs off reliever Jeff Manship. Manship, who was optioned to Triple-A Rochester after the game, gave up RBI singles to De Aza, Youkilis and Dunn that frame.
Minnesota scored one more run against Sale in the sixth, as Denard Span tripled and scored on a sacrifice fly from Ben Revere.
"Finding a rhythm early always helps," said Sale, who is 9-2 with a 2.27 ERA. "They scratched a few off on me in the middle of the game. But when you get run support like I did today, it was nice."
It was all the Twins could do against Sale, who surrendered just those two runs on six hits and a walk over seven strong innings. The left-hander also struck out five.
"He's got some funk to it," said Justin Morneau, who went 1-for-4. "His breaking ball, for it to go for a strike, pretty much has to start behind you. And he's got pretty good feel for it also; when he needs to get a strike with it, he can. And when he's ahead in the count and feels he needs to get you to chase, he's got that one. He has plus-velocity and reach back for 95 mph when he needs it. So it makes it tough to stay back with a 15-20 mph difference."
In the eighth, the Twins' Darin Mastroianni hit his first Major League homer, a two-run shot off lefty Will Ohman. Minnesota also scored a run in the ninth against Ohman on an RBI groundout by Dozier with the bases loaded.
But Chicago kept adding late runs, scoring a run off Jeff Gray in the seventh and two more in the eighth against Tyler Robertson.
"I looked up in the eighth inning and they'd scored in six of eight innings, and that doesn't bode well," Gardenhire said. "Couple of big numbers."