The Australia international sustained the injury to his left knee in training and will go under the knife next week.
As well as ending his season, the injury looks likely to cost him a place at the FIFA World Cup in Brazil with Australia.
A Leverkusen statement read: "Robbie Kruse suffered a tear of the anterior cruciate ligament in his left knee in training and thus is likely to be missing for Bayer 04 in the entire second half of this season.
"The Australian International picked up the injury on Friday at training, today (Saturday) an MRI scan showed the worst results."
Kruse moved to the BayArena from Fortuna Dusseldorf in the close-season and has made 21 appearances for Leverkusen this season, scoring three goals.
Sami Hyypia's side will resume their Bundesliga camapign at Freiburg next Saturday, sitting second in the German top flight.
