Morsy sustained the injury during the goalless draw at Bristol Rovers at the end of last month and scans have shown that the midfielder has a torn medial cruciate ligament.
Spireites boss Paul Cook said: "It doesn't look good for Sammy, he's not going to be back before the beginning of the new year.
"It's a big blow but that's football, injuries are part and parcel of the game.
"It's disappointing because not only is he a good player, and I feel he's going to be a very, very good player because he has all the right attributes, the right attitude, and that little bit of devilment in him, but he's good in the dressing room too - he's a winner.
"There's not too many of them around in football now, a lot of lads generally just turn up, play and go home. But it hurts Sammy. The run we are on hurts Sammy, and it's hurt all our players bad."
Chesterfield head into Saturday's FA Cup first-round tie against non-league Daventry without a league win in seven matches.