Gonzalez came out to warm up before the Reds' at-bat in the sixth, but was soon surrounded by Astros infielders, a few coaches and trainers.
After a brief conversation on the mound, Gonzalez left the game and was replaced by Wesley Wright.
"I really felt good the whole game," Gonzalez said. "Just in the fifth inning, I got a blister [on] my foot. I just talked to Tony and said 'You know what? I'm Mexican. I can try. Let me go.' But he said, it was 'better for the next game if we take you out.' So he took me out."
Gonzalez tossed five innings and gave up one run on two hits with one walk and six strikeouts. He threw 79 pitches and helped the Astros gain a 5-1 lead en route to his second win of the season.
In his previous outing on Monday -- his first start since 2009 -- Gonzalez lasted 5 1/3 innings against Pittsburgh, allowing one run on five hits. He threw 82 pitches before exiting that game.
Astros interim manager Tony DeFrancesco said the trainers tried to wrap the blister up between innings, but ran out of time and had to turn to the bullpen.
"It's just a blister, they'll take care of it," said DeFrancesco, who assured Gonzalez would be ready for his next start. "We really didn't have time to fix it. They tried to get it on the bench, but there wasn't enough time. They were still getting his shoe back on, and the guys were taking care of it."
Mark Clements is an associate reporter for MLB.com. This story was not subject to the approval of Major League Baseball or its clubs.