Dayan Viciedo finished 3-for-5 and drove in two runs as Chicago edged Minnesota, 4-3, in the second edition of a three-game set.
Alejandro De Aza added two hits and scored twice, while Marcus Semien and Alexei Ramirez knocked in a run apiece for the White Sox, who have taken the first two in the series after losing six in a row.
Jose Quintana (8-6) allowed eight hits and one run, fanning five with just two walks over six innings.
"He just continues to battle all game and continues to find a way to get through innings," said Chicago manager Robin Ventura about Quintana.
Trevor Plouffe collected two hits and two RBI for the Twins, who have dropped six of seven. Brian Dozier contributed three hits and two runs scored in defeat.
Mike Pelfrey (5-13) struck out six, but was charged with nine hits and three runs over 4 1/3 frames.
"It's definitely not how I thought I was going to finish the year," said Pelfrey. "I should be able to get one more so hopefully I'll be able to go out on a positive note."
The Twins managed to reduce their deficit from three to one in the seventh. Facing Jake Petricka, Darin Mastroianni walked, then advanced on a wild pitch, moved to third on a Dozier single and scored on a Plouffe single. Dozier then scored on Oswaldo Arcia fielder's choice grounder against Donnie Veal. Matt Lindstrom later stranded runners on the corners by fanning Josh Willingham and inducing a groundout from Josmil Pinto.
Nate Jones tossed a scoreless eighth and Addison Reed followed suit in the ninth to record his 38th save.
Gordon Beckham singled with one away in the second, went to third when Josh Phegley singled and scored on a Semien base hit.
Minnesota countered in the third when Plouffe doubled home Dozier, who reached on a fielder's choice and stole second.
Chicago moved ahead by a 3-1 count in the fifth after an RBI double from Ramirez and run-scoring hit by Viciedo, then assumed a three-run edge in the next at-bat after Viciedo drove home De Aza with a two-out single.
The White Sox have won eight of 18 meetings this season over Minnesota, and three of eight on the south side ... Quintana picked up his first win since Aug. 16 at Minnesota, having lost twice with three no-decisions since then.