Both teams will get their first shot at reversing those fortunes Monday night when they open a three-game series at Coors Field.
Colorado (3-4) certainly has endured its share of struggles against AL opponents in recent seasons, dropping 28 of 35 meetings - including 16 of 19 at home - the past two seasons.
The Rockies went 5-15 overall in those matchups in 2013 on the way to their second straight last-place finish in the NL West. They went 42-29 with a 4.35 ERA at home against NL foes, but finished 3-7 with a 5.04 mark there when facing the AL.
Jordan Lyles will try to get the Rockies off to a good start in interleague play as he takes the mound for the second time since coming over in the December trade that sent Dexter Fowler to Houston.
Lyles, however, has gone just 6-12 with a 5.63 ERA in 26 career starts against AL opponents. In his only start against the White Sox (3-3), he coughed up five runs over 4 1-3 innings in a 10-1 road loss June 9, 2012, while with the Astros.
The right-hander managed to get a win in his Colorado debut despite allowing four runs in five innings of a 6-5 victory in Miami on Wednesday. Now he'll have to deal with a Chicago lineup that has hit .278 while averaging 5.7 runs.
That kind of production was lacking last season when the White Sox scored just 3.4 per game while losing eight of 10 interleague road games en route to the AL Central cellar. Their starting pitchers also scuffled in those matchups, posting a 5.66 ERA.
Felipe Paulino hopes to give Chicago its second straight outstanding performance after Chris Sale gave up four singles in eight scoreless innings in a 5-1 win at Kansas City on Sunday.
Flowers hit .195 last season in 275 plate appearances.
"My stance is completely different," Flowers told the league's official website. "I feel like my swing is a whole lot different. All and all, I feel like almost a different player."
Flowers was behind the plate Wednesday as Paulino pitched well in his first start since June 6, 2012, because of back and elbow surgeries. The right-hander allowed one earned run over 5 1-3 innings in a 7-6, 11-inning home win over Minnesota.
Paulino, who spent the 2010 season with Colorado, has surrendered 16 runs and 26 hits over 18 1-3 innings in nine career games - two starts - at Coors Field.
After totaling 21 runs while winning the first two games of the series, the Rockies hit into five double plays in a 5-3 home loss to Arizona on Sunday. Charlie Blackmon, who went 9 for 10 in the two victories, went 1 for 4 with an infield single in the finale.
"We were not able to get any rally going," said Carlos Gonzalez, who is 9 for 26 after going 1 for 4 Sunday.
Michael Cuddyer, hitting .433 on the season, has batted .297 with 19 home runs in 145 career games against the White Sox.
Chicago has won five of six meetings in Colorado, last taking two of three in June 2011.