The 40-year-old Pettitte suffered a a fractured left fibula in Wednesday's win against the Cleveland Indians after getting struck on the left shin with a line drive.
Pettitte, who will not undergo surgery, is not eligible to return from the DL until Aug. 28. General manager Brian Cashman, appearing on "The Michael Kay Show" on ESPN New York 98.7 FM on Thursday afternoon, said he expected Pettitte to be out until about Sept. 1.
Pettitte's injury occurred hours after the Yankees placed ace CC Sabathia on the disabled list because of a strained muscle in his leg.
Although Major League Baseball's non-waiver trade deadline is just more than one month away, the Yankees will look to handle the losses of Pettitte and Sabathia from within, sources told ESPN The Magazine's Buster Olney.
"I'd prefer not to go outside," Cashman said. "Obviously, we do go outside. We have done that before. This is part of the process."
Adam Warren make his major league debut on Friday for the Yankees against the Chicago White Sox.
Pettitte hasn't pitched a full season since 2009. In 2010, he only made 21 regular-season starts because of injuries. Last year, he sat out after his retirement announcement.
After cruising through the first four innings against Cleveland, Pettitte was struck on the lower leg by a liner off the bat of Casey Kotchman. He tried to recover the ball before crumbling to all fours. Yankees manager Joe Girardi and trainer Steve Donohue attended to Pettitte, who attempted to stay in the game after a brief discussion and a few practice pitches.
But after throwing one pitch to Lou Marson, Pettitte winced and hobbled off to the dugout, unable to continue.
"I've been hit in the shins so many times and I've never had to come out of a game," Pettitte said. "I just thought I would get on the mound and eventually it is going to go away."
Since returning from retirement less than two months ago, Pettitte has been one of the Yankees' better starters. He entered Wednesday with a 3-3 record and a 3.22 ERA. With his seven strikeouts on Wednesday, he has struck out at least six in his last five starts, tying the longest stretch of his career.
"He's been awesome," Cashman said.
Information from ESPNNewYork.com's Andrew Marchand and Wallace Matthews was used in this report.