The 32-year-old number eight was rested for Australia's win over Argentina on Saturday after suffering a heavy clash during victory over the Springboks the week before.
It was decided not to risk his recovery for the tour to South Africa and Argentina, a team spokesman said on Monday.
Ben McCalman replaced Palu in the starting side against Argentina, with Scott Higginbotham on the bench.
The Wallabies will also travel to South Africa without hooker Tatafu Polota-Nau who was restored to the side against Argentina after a long layoff with a knee injury only to hurt an ankle during the match.
Winger Peter Betham is also in doubt for the rest of the season after aggravating a foot injury against the Pumas, though utility back Adam Ashley-Cooper is likely to be fit to play after resting with a neck injury.
Australia lie third in the four-nation southern hemisphere tournament with two rounds to play, level with second-placed South Africa on 10 points but six behind champions New Zealand.
The Wallabies play the Springboks in Cape Town on Sept. 27 followed by the Pumas in Mendoza a week later.
(Reporting by Ian Ransom; Editing by Ed Osmond)
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