Corbisiero had been expected to return to the starting line-up after missing the first Test and coming off the bench in the second.
Head coach Stuart Lancaster has announced the London Irish forward will be replaced in the side for the final game against the Springboks by Harlequins' Joe Marler.
Corbisiero, 23, established himself as first-choice loosehead during this year's Six Nations Championship but then missed the end of the domestic season after a biceps operation.
He was fit enough to join the England squad for the South Africa tour but jarred his knee in training soon after arrival in the country.
His place for the first Test in Durban went to Marler and the Quins forward retained the starting spot in Johannesburg last week.
Corbisiero was set to return in Port Elizabeth as Lancaster initially named a team featuring six changes but 21-year-old Marler, who was perhaps unlucky to be dropped, will now be retained.
England are looking to claim a consolation victory at the Nelson Mandela Bay Stadium after defeats in the first two matches.
Lancaster said: "Alex trained well early in the week having played well at the weekend but the knee reacted over the last 24 hours.
"It is a shame for Alex as he was desperate to take part but it's the right thing to put in Joe and we are sure he can build on his performances in the first two Tests."
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