Houston changed that quickly, and Pelfrey and the Minnesota Twins couldn't recover.
Pelfrey (6-9) was tagged for seven runs and eight hits with five strikeouts in four innings. It was Pelfrey's second straight outing of four innings or less — both against the Astros.
"These guys kicked my butt five days ago," Pelfrey said. "They did it again today. It was even worse today."
Pelfrey lasted just 3 2-3 innings in his last start against the Astros on Saturday, allowing four runs in a 4-1 loss.
"I think he has to be more effective with the fastball in terms of where he's putting it, backing them off here and there, whatever he needs to do," Twins manager Paul Molitor said. "But, there are just a lot of aggressive swings against the fastball."
Pelfrey said he thought his stuff was OK, but it wasn't good enough.
"I feel good," he said. "I'm healthy. The results just haven't been there. I'm going to keep plugging away and keep going and hopefully, it will turn around soon."
Colby Rasmus had two hits, including a monstrous two-run homer into the upper deck in right field in the second inning to give the Astros a 3-0 lead.
Pelfrey had not given up a home run since July 22 at the Los Angeles Angels before Rasmus' blast, a span of 42 2-3 innings.
"Usually, I do a better job of keeping the ball in the park, and I was unable to do that tonight," Pelfrey said. "I put the team in a pretty big hole for a guy on the mound that's having a pretty good year. I made it pretty tough on us."
Conger upped the lead to 7-0 with the grand slam in the fourth into the Crawford Boxes in left field. After Evan Gattis, Jed Lowrie and Carlos Gomez led off the inning with singles, Pelfrey struck out the next two hitters to set up Conger's second grand slam of the season.
"It was tough because he was close to getting out of that jam with a couple strikeouts and then he fell behind Conger," Molitor said. "The grand slam was a separator there."
Conger, who had not hit a grand slam before this season, hit his first career grand slam Aug. 1, against Arizona. He added an RBI single in the eighth.
In four of his last six starts, Pelfrey has lasted less than four innings.
"I think right now he's struggling a bit confidence-wise," Molitor said. "The results haven't been good as of late. . I'm not sure if it's a late season thing as much as he's just not heading in the right direction his last couple starts."
Joe Mauer had two hits and the best chance to score for Minnesota but was thrown out at home by Gomez trying to score on Miguel Sano's single in the first. The Twins did not get a runner past second base the rest of the way.
McHugh (15-7) gave up seven hits and struck out six in picking up his second straight win. McHugh has allowed two runs or fewer in each of his last six starts.
Carlos Correa's RBI fielder's choice in the first gave Houston a 1-0 lead.
Lowrie had three hits and scored twice, and Gattis had two hits for Houston.
Twins: RHP Phil Hughes (lower back inflammation) is expected to throw off a mound in Minneapolis this weekend and will join the club in Kansas City for a simulated game next week.
Astros: OF George Springer was activated from the 15-day DL on Friday and started in right field. Springer went on the DL with a right wrist fracture on July 2. He went 1 for 4 with a single.
TEN ASTROS WITH TEN HOMERS
The grand slam was Conger's 10th home run of the season, giving the Astros 10 players with 10 or more home runs, breaking the franchise record of nine set in 2000. The major league record is 11 players with 10 or more home runs set by the Detroit Tigers in 2004.
Twins: RHP Ervin Santana (3-4) goes Saturday in the second game of the three-game series. Santana threw seven shutout innings with 10 strikeouts in his last start Sunday against the Astros.
Astros: RHP Lance McCullers (5-5) matches up for a second straight start against Santana after taking the loss Sunday, giving up three runs in six innings.