Pettitte, 40, was injured Wednesday when he was hit by a batted ball. The injury was diagnosed as a fractured left fibula and doctors said he will need to use crutches and wear a protective boot while recovering.
Pettitte ended a one-year retirement and rejoined the Yankees in March. He was 3-3 with a 3.22 earned run average in nine starts this season.
Pettitte has pitched in the majors for 17 seasons, 14 of them with the Yankees. He had a career record of 243-141 with a 3.87 ERA. He was selected to three all-star teams, including during the 2010 season.
He was injured the same day the Yankees placed pitcher CC Sabathia on the 15-day disabled list.
New York has called up right-handers Adam Warren and Ryota Igarashi from Triple-A Scranton/Wilkes-Barre to take the open roster spots.