Both home runs by Plouffe were solo shots, but each gave the Twins a lead. His first blast came in the fourth inning and staked Minnesota to a 1-0 lead. It was his 19th of the season.
It was Plouffe's turn again in the eighth, putting the Twins on top with his second homer of the night and 20th of the season.
Plouffe finished 3-for-5 with the two home runs and three RBIs.
Minnesota tacked on three more in the ninth, highlighted by a home run from Eduardo Escobar and an RBI single from Plouffe.
Hunter also got it done at the plate he was 2-for-5 with a double and an RBI.
Ervin Santana (5-4) held the White Sox to two runs on six hits in seven innings. Santana struck out six in the game.
He had some help from the Twins defense. Hunter threw out a pair of White Sox runners, including one at the plate in the 4th.
Tommy Milone (8-4) takes the mound for the Twins Saturday evening against Chicago's Jose Quintana (8-10).