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Leach suffered the injury during England's first Test victory in Hyderabad before sitting out the second Test as India levelled the series in Visakhapatnam.
The 32-year-old, who has played in 36 Tests, was by far the most experienced member of an England spin attack featuring teenager Rehan Ahmed, recent debutants Tom Hartley and Shoaib Bashir and the part-time bowling of Joe Root.
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With the third Test due to start in Rajkot on Thursday with the series tied at 1-1, England have confirmed they will not call up a replacement for Leach.
"England and Somerset spinner Jack Leach has been ruled out of the rest of England Men's Test tour of India with a left knee injury," an ECB statement released on Sunday said.
"Leach sustained the injury during England's first Test victory in Hyderabad and missed the second Test in Vizag as a result.
"He will fly home from Abu Dhabi in the next 24 hours, where the England team have been staying ahead of the third Test in Rajkot, which starts on Thursday.
"Leach will work closely with the England and Somerset medical teams in respect of his rehabilitation."
Leach has been plagued by injuries and health issues since making his England debut in 2018, with the series-opener in India his first Test appearance since suffering a stress fracture to his back in June last year.
While India are without key batter Virat Kohli due to personal reasons, Leach's absence in a series where England are largely relying on spin severely stiffens the task facing Ben Stokes' side.
The fourth Test follows in Ranchi on February 23, before the series finale begins in Dharamsala on March 7.
England Test series in India 2024
- First Test, Hyderabad: England beat India by 28 runs
- Second Test, Vizag: India beat England by 106 runs
- Third Test - February 15-19 (Rajkot)
- Fourth Test - February 23-27 (Ranchi)
- Fifth Test - March 7-11 (Dharamshala)
Follow over-by-over text commentary from the third Test between India and England, in Rajkot, from Thursday live on skysports.com and the Sky Sports App (first ball at 4am).
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