Verlander struck out six -- including all three in the first inning -- and allowed three hits and one walk to the visiting Baltimore Orioles before departing his shortest outing of the season. The game was scoreless at the time.
"He's going in for some imaging [Monday]," Houston manager Dusty Baker said. "He felt that -- when he was covering first base -- that it was his calf. And that is the best of bad news. We were really glad that it wasn't anything to do with his arm or elbow or anything like that."
Astros reliever Seth Martinez started warming up in the bullpen while Verlander was still on the mound, and he entered the game to start the fourth inning after throwing 16 pitches on Saturday.
Martinez, who worked one inning, was one of five relievers to carry the Astros the rest of the way. Ryne Stanek (2-1) also worked an inning and was awarded the win in Houston's 3-1 victory. The Astros' bullpen picked up where Verlander left off, striking out seven Orioles in six innings.
Verlander has had a terrific season as Houston has comfortably sat in first place in the American League West for most of it. The 39-year-old veteran entered Sunday's start with a 16-3 record, a 1.87 ERA, a 0.85 WHIP and 148 strikeouts.
"These things happen," Baker said. "They can happen to anyone on the field. I'm just glad it wasn't his arm."
Verlander opened the third by allowing an infield single to Robinson Chirinos and a walk to Cedric Mullins. He escaped with a strikeout of Adley Rutschman before inducing a double play off the bat of Anthony Santander.
"When he came off the field, after he threw that last pitch, he just went right down into the tunnel, and said he felt something," Baker said.
The Associated Press contributed to this report.