The England and Wales Cricket Board said vice-captain Ollie Pope would lead the team in the match at the Oval starting Thursday, with England 2-1 up in the series.
All-rounder Stokes has struggled with various fitness issues in the four Tests against India so far, during which he has sent down 140 overs – the most he has bowled in any series.
The 34-year-old, who is the leading wicket-taker on either side with 17 scalps, has injured his right shoulder – his bowling arm – and it is understood he could need up to 10 weeks to recover.
“I am obviously disappointed to not be able to finish the series,” an emotional Stokes told reporters on Wednesday.
He added: “I have got a decent tear of one of the (shoulder) muscles I can’t pronounce. A bit of emotion goes into this kind of stuff when you find out what you have done – bowling was ruled out as soon as we got the scan results.”
The drawn fourth match of the series at Old Trafford, which ended on Sunday, was a personal triumph for Stokes, who became just the fourth England cricketer to score a hundred and take five wickets in the same Test.
But that came at a cost as the talismanic all-rounder, whose career has been blighted by hamstring trouble, struggled with a number of fitness issues.
India lost just four wickets in their second innings as they batted out a marathon 143 overs to keep the series alive. (AFP)