Starc and Hazlewood would be stood down to allow them time to refresh ahead of the Australian summer season, CA said.
"Mitchell and Josh have had big tours of Sri Lanka and have a heavy workload ahead of them with ten Tests to be played this (domestic) summer," chief selector Rod Marsh said.
"As such, it is important they are managed appropriately and we believe missing the tour of South Africa is the right time for them to take a break."
Marsh said that with a number of bowlers returning from injury, it was important for the national team to continue to build up a battery of quality fast-bowlers.
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Earlier this week Australian paceman Nathan Coulter-Nile was ruled out for an indefinite spell after returning home early from the Sri Lanka ODI series with a serious back injury.
CA said Hazlewood would return home immediately from the tour of Sri Lanka and Starc would remain with the side for the remaining ODI and two T20 Internationals against Sri Lanka.
The tour consists of one ODI against Ireland and five against South Africa, with the first match to be played against Ireland on September 27.
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