Loaiza, who was aiming for his eighth win and to once again end a Sox' skid, gave up one run in six innings, lowering his ERA to 1.99.
After the game, the Sox fired hitting coach Gary Ward.
The Sox jumped in front to a 2-0 lead off the Twins and Kyle Lohse with Valentin's ninth homer of the season, a two-run shot in the third inning.
They relied on that lead far too long, failing to score on a base-loaded situation in the fifth and a first and third, one out opportunity in the seventh. Magglio Ordonez grounded out to end the fifth and Frank Thomas hit into a double play to end the seventh.
A Todd Sears RBI-single in the fifth cut the lead to 2-1, and the eighth inning debacle put the Twins on top. Damaso Marte pitched a scoreless inning of relief in the seventh.
With one out, Torii Hunter and Dustin Mohr both singled to put men on the corners off Tom Gordon, who then threw a wild pitch, allowing Hunter to score the tying run.
Two batters later, after intentionally walking Bobby Kielty, AJ Pierzynski hit a grounder to Paul Konerko at first. After getting the force out at second, Valentin made a throwing error on the double play attempt at first, allowing the winning run to score.
The Sox threatened in the ninth inning with Joe Crede getting a walk and D'Angelo Jimenez beating out an infield single, but Tony Graffanino struck out to end it, giving Eddie Guardado his 10th save.
The Sox will now go back to U.S. Cellular Field and host the Toronto Blue Jays to a three-game set starting Monday at 7:05 p.m. CT. Danny Wright is scheduled to start against Corey Lidle.