The 21-year-old will have surgery on Tuesday after tearing a knee ligament in the weekend defeat to Hannover
The Bosnia-Herzegovina international was forced from the field 16 minutes into Saturday's 2-1 defeat at the hands of Hannover in Schalke's opening Bundesliga match of the season.
Subsequent tests revealed a tear and Kolasinac is expected to undergo surgery on Tuesday, according to a statement released by the club via their official website.
The 21-year-old, who featured twice for his country at the World Cup in Brazil, made 24 league appearances for Schalke last season.
In April, Kolasinac claimed he had received an offer from Manchester United, who have since signed Luke Shaw and Marcos Rojo.
Schalke take on reigning Bundesliga champions Bayern Munich next Saturday in their second game of the new season as they look to bounce back from a disastrous start to 2014-15.
Jens Keller's side were stunned by Dynamo Dresden in the DFB-Pokal before Saturday's defeat by the same scoreline to Hannover, but general manager Horst Heldt insists it is too early to panic.
"If you lose twice in a row, then it is something you can unfortunately not avoid," he said. "We must stand [together] as Schalke.
"But what is important is what is being discussed internally with us. We do not discuss the coach.
"The good thing about football is that a season is not already decided after the first matchday."