"A medical examination this evening showed a cruciate and interior ligament tear in the right knee," Schalke said in a statement.
"The left-footer is expected to miss the rest of the season."
Already without a string of key players, including striker Klaas-Jan Huntelaar and central defender Kyriakos Papadopoulos, Aogo's injury could not have come at a worse time for sixth-placed Schalke who are looking to improve their league form.
Midfielders Jefferson Farfan (groin) and Kevin-Prince Boateng (knee) have also been forced to sit out games in recent weeks due to nagging injuries.
Schalke are hoping to book their spot in the Champions League knockout stage by beating Basel in their last group phase match on December 11.
Schalke are third in Group E, a point behind the Swiss team with Chelsea in top spot.
The Germany international, who is on loan at Schalke from Hamburg SV, had also been hoping to catch the eye of national team coach Joachim Loew ahead of next year's World Cup finals.
He won the last of 12 international caps against the United States in June.
(Reporting by Karolos Grohmann; editing by Toby Davis)
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