The 2019 winner will take no further part in the Springboks’ defence of the Webb Ellis Cup, after suffering ligament damage in training on Wednesday and being sent for scans.
South Africa launched their World Cup defence with a punishing 18-3 victory over Scotland in Marseille on Sunday, but must now move on without one of their outstanding front-row forwards.
South Africa do not plan to replace Marx with another hooker, but confirmed they will announce a new addition to their squad later this week.
Marx’s injury represents a major blow to the Springboks, with the 29-year-old a key member of South Africa’s famed “Bomb Squad” twin front rows.
Former Leicester flanker Marco van Staden has been training at hooker and will add extra cover to the position alongside regulars Bongi Mbonambi and Deon Fourie.
“First and foremost we are extremely disappointed for Malcolm, and we wish him all the best in his recovery,” said Springboks head coach Jacques Nienaber.
“He’s been working very hard to be in the best form possible for the tournament, and it’s tragic that his campaign has ended this way.
“As a team we will remain in contact with him, as we do with all injured players like Lukhanyo Am, Handre Pollard and Lood de Jager, and support him as much as we can through the recovery process.
“We have enough cover at hooker with Bongi Mbonambi and Deon Fourie in the squad, while Marco van Staden has also been training there and has been named on all our team sheets so far as a hooker option.
“We’ll assess our needs for the rest of the tournament and confirm who we are calling up as an additional player later this week.”
South Africa will face Romania in their second Pool B clash on Sunday in Bordeaux, before a blockbuster showdown with Ireland in Paris on September 24. They conclude their campaign against Tonga in Marseille on October 1.