Cricket South Africa (CSA) revealed Chris Morris has been managing the problem for the majority of 2016 and has been encouraged to take a break in order to recover.
Dwaine Pretorius, previously uncapped, will replace the 29-year-old for the series against Australia that begins at Centurion on September 30.
However, it is hoped Morris will be available for selection when the Proteas face Sri Lanka in a three-match Test series starting on December 26.
“Chris has been carrying a chronic left knee patella tendon injury for the last eight months which we have treated and managed up to this point,” said South Africa team manager Mohammed Moosajee in a CSA release.
“The injury has flared up considerably over the last two weeks leaving us with no option but rest and rehabilitation to allow the knee time to fully recover.
“He will take no further part in the match against Ireland [on Saturday] and the series against Australia and will target a return back to international cricket for the Test series against Sri Lanka in December.”