A waiver wire pickup from the Colorado Rockies before the 2014 season, McHugh put it all together upon his arrival in Houston. Collin recorded a 2.73 ERA in 154-2/3rd innings and averaged more than a strikeout per inning to finish fourth in the balloting for the 2014 American League Rookie of the Year Award.

McHugh ended the season on a personal seven-game winning streak and added to that total by winning his first four decisions in 2015. McHugh finished his second season in Houston with a 19-7 record and a 3.89 ERA, placing eighth in the A.L. Cy Young Award voting.

The Naperville, IL righthander went 13-10 the next year and 5-2 in 2017 before injuries curtailed his season. He was sent to the bullpen in 2018, posting a 6-2 record with a 1.99 ERA then returned to the rotation in 2019 only to have his season end after eight starts.

Through the 2019 season, McHugh has posted a 58-43 record with a 3.95 ERA.