Pence left Wednesday night's game at the Atlanta Braves after injuring his hamstring for the second time in two weeks.
He stopped about halfway down the first-base line after hitting a slow grounder to third base in the fourth inning and grabbed the back of his leg as he leaned over.
"Unfortunately [Pence] did a pretty good job on it," Giants manager Bruce Bochy told reporters Thursday morning. "That's a shame."
Outfielder Mac Williamson was recalled from Triple-A Sacramento to take Pence's roster spot.
Pence, who is tied for the team lead with seven homers and leads the Giants with 36 RBIs, returned to the lineup Saturday after not starting in six straight games with a right hamstring injury.
The Associated Press contributed to this report.