The Astros will attempt to end Hughes' run of six consecutive victories and claim their sixth straight road win Friday night.
Hughes (6-1, 3.12 ERA) has a 1.99 ERA during an unbeaten streak that's spanned eight starts. His six wins in a row have matched the second-longest streak in the majors this season and trail Kyle Lohse's seven for Milwaukee.
Hughes won nine consecutive decisions from Aug. 14, 2009-May 12, 2010, while with the New York Yankees. He earned his latest win against his former club on Sunday by allowing two runs and three hits in a season-high eight innings.
He's faced the Astros only once in his career on June 13, 2010, and got enough support for a 9-5 victory. Hughes gave up five runs in 5 2-3 innings.
This year's Houston team is on track to accomplish something it hasn't since that 2010 season, avoiding 100-plus losses. The Astros (26-35) have helped themselves by performing well offensively in their recent games away from home.
Houston is batting .328 and has scored 34 runs in five consecutive road wins, one shy of matching its best run in 2013. The Astros have produced at least 11 hits in each of those contests and had 10 apiece in its two home wins against the Los Angeles Angels this week.
Houston finished off that three-game set with an 8-5 victory Thursday and rookie George Springer drove in three runs, giving him 32 RBIs in 44 games.
"''The hitters are doing their job. The pitchers have been doing tremendous. We have been playing really good defense," second baseman Jose Altuve said. "It seems like we are putting everything together."
Altuve went 2 for 5 with two RBIs and is batting .370 while hitting safely in 25 of his last 27 games. He hit .348 in his five games last year against the Twins, and the Astros batted .270 overall in their six matchups - their second-best average against any opponent in 2013.
Houston, though, went 1-5 in those games and was swept in its three at Target Field from Aug. 2-4.
Minnesota hoped to enter this series on a three-game win streak and at .500, but blew an early 4-0 lead in Thursday's 8-5 loss to Milwaukee.
The Twins (28-30) had won four of six before their fifth defeat in seven home games.
"It was a very frustrating game," manager Ron Gardenhire said. "We made some bad pitches and some bad baserunning decisions."
Dallas Keuchel (6-3, 2.70) will try to send Minnesota to another loss at Target Field while rebounding from the end to a four-game win streak. The left-hander gave up three runs over six innings to Baltimore on Saturday and didn't get his usual robust support in a 4-1 defeat.
Keuchel posted a 1.05 ERA in his four consecutive victories and was given a combined 21 runs to work with.
Keuchel is making his first start against Minnesota. Jason Kubel has a pair of home runs in three at-bats against the left-hander, but he's 0 for 22 with 10 strikeouts in his last eight games.
The Twins are hoping to get Oswaldo Arcia back after he was forced to leave Thursday's loss with a sprained right ankle. Arcia, who hit Minnesota's first grand slam of the season before leaving, has two homers and eight RBIs in his last two games.