McHugh (2-0) followed up his first outing where he struck out 12 and allowed three hits in 6 2-3 innings at Seattle on Tuesday with another dominant performance.
He struck out seven and walked three, allowing one run in the longest outing of his career. His previous longest outing had been seven innings on Aug. 23, 2012 against Colorado when he was a member of the New York Mets.
After the first, McHugh retired 23 of the next 24 batters, including 19 straight before Brandon Moss was hit by a pitch with two outs in the ninth. Moss stole second and came around to score on Alberto Callaspo's single — McHugh's first run allowed in 15 1-3 innings this season.
Raul Valdes got the final out to complete the two hitter.
Jed Lowrie, who singled in the first inning, drew a walk in the third for McHugh's lone base runner until the ninth.
The right-hander, who Houston claimed off waivers from Colorado during the offseason, got out of trouble in the first after loading the bases with two outs with a walk to Callaspo by getting Josh Reddick to pop out to end the inning.
Jose Altuve had two hits, including a two-run home run in the seventh, and Jonathan Villar also had two hits, including a two-run triple.
Tommy Milone (0-2) allowed four runs on five hits with two strikeouts in 6 2-3 innings. The left-hander was just effective for most of the day, retiring 12 out of 13, including nine in a row, but he ran into trouble in the seventh.
Villar extended the lead to 3-0 with a two-out, two-run triple to the left centerfield gap in the seventh, scoring Matt Dominguez and Carlos Corporan and ending Milone's day. Altuve greeted Dan Otero with a two-run home run to the Crawford Boxes in left to up the lead to 5-0.
Dexter Fowler gave the Astros a 1-0 lead in the third with a groundout scoring Villar, who had doubled with one out and reached third on an Altuve single.
NOTES: Oakland outfielder Yoenis Cespedes was out of the lineup for the third straight game with a strained left hamstring. Cespedes left in the seventh inning of Oakland's 10-1 win over Houston on Thursday after legging out an infield single. ... Houston right-handed pitcher Scott Feldman, who has been on the 15-day disabled list retroactive to April 18 with right bicep tendinitis, threw Saturday and was fine and was on track to make his next scheduled start, manager Bo Porter said, adding that could be either May 3 or May 4. Feldman is eligible to come off the DL May 3. ... Oakland challenged and won the replay in the ninth on Moss' hit by pitch. The initial ruling was that it was a ball, but the call was overturned and replay showed that it hit Moss' foot.