In addition, the Browns also lost defensive end Armonty Bryant to a knee injury -- believed to be a torn ACL. He will need surgery and miss the rest of the season.
Coach Mike Pettine said that if Mack has only a broken leg, the timetable for his return would be eight to 10 weeks. If there is anything more than a broken leg, he would be done for the season.
The team isn't sure, but Pettine said it looks like Mack will be done for the season.
"It's tough," Pettine said. "It's not just losing his play but it's also an emotional letdown as well. A guy who exemplified everything you're trying to get done."
Mack went to his first Pro Bowl a year ago and was off to an excellent start this season. He had not missed a snap for the Browns until he was injured in the second quarter of the win over the Pittsburgh Steelers -- a streak of 5,279 in a row.
The team reported his surgery would be done in the next few days, with a firm timetable for his recovery determined after surgery.
"Like coach told us in the meeting, you don't replace Alex Mack," quarterback Brian Hoyer said. "A guy who's never missed a snap in his NFL career. Pro Bowl center. You don't replace that guy. But I think that as you saw (Sunday), John Greco steps in, never -- I didn't know this until after the game -- played center in an NFL game.
"You look at his first play, Pittsburgh tested him. They brought a blitz right up the middle and he made a great call, great block. Paul McQuistan comes in and does a great job filling in. Those guys are going to do everything they can to step in and step up, but everyone knows what Alex means to this offense."
In his absence, Greco slid from right guard to center and McQuistan took over at guard. It's expected the Browns will continue with that alignment, though that was Greco's first NFL snap at center.
Bryant was injured on a Steelers' run in the first quarter. While trying to make a tackle, players rolled behind his legs and his right foot was caught under a pile, which put too much torque on his knee.
Bryant had impressed this season's coaching staff with his pass-rush ability. The Browns will miss him most in that area.
Pettine said the Browns likely will make a move to add a defensive lineman.
"(Bryant) will be difficult to replace," Pettine said. "He's one of our most productive pass rushers."