Moore will also miss Australia's final Rugby Championship fixture against Argentina in Rosario on October 7.
The 29-year-old is equal with Jeremy Paul on 72 caps and was in line to become the most capped hooker in Australian rugby history.
Moore strained his hamstring in Australia earlier this month, missing the home Tests against South Africa and Argentina, and aggravated the injury at training on Monday in Johannesburg.
Uncapped hooker James Hanson has flown to South Africa as cover, while Tatafu Polota-Nau is set to start against the Springboks and Saia Faingaa will sit on the bench.
Meanwhile, the Springboks remain confident that centre Francois Steyn will be fit enough to play on Saturday.
Steyn hurt his right ankle in training on Monday but has responded well to treatment and will be given every opportunity to prove his fitness.