The 32-year-old pulled up with a hamstring strain during the first Test at Lord’s and only played a minor part in his side’s drawn match against Northamptonshire on Saturday.
"Zaheer Khan is suffering from a recurrent right hamstring strain and a right ankle impingement,” read a statement from the Indian cricket board.
"He will need at least 14-16 weeks to recover completely. He will require surgery for his ankle, followed by intensive rehabilitation for both the ankle and hamstring."
"He will therefore not be able to participate in the ongoing Test series and subsequent T20 International and ODI series against England,” they added.
The tourists are without Harbhajan Singh and Yuvraj Singh for the remaining two Tests of the series, which England currently lead 2-0, and victory in the third Test, which starts Wednesday at Edgbaston, will put the hosts at the top of the ICC world rankings.