Selectors included Victorian Chris Tremain and South Australians Joe Mennie and Daniel Worrall in a 15-man squad after deciding to rest Starc and Hazlewood after the recent Test and ODI series in Sri Lanka.
Starc and Hazlewood have been given time off to refresh ahead of the Australian summer season, while Usman Khawaja, Moises Henriques and Nathan Lyon were left out of the South Africa-bound squad.
"Chris, Joe and Daniel all had terrific summers last year and have also impressed us during the recent Australia A series with consistent performances," chief selector Rod Marsh said.
"We look forward to seeing them work with John Hastings and Scott Boland, who have both performed well for Australia since returning from injury."
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Captain Steve Smith, who was rested from the Sri Lanka tour after the second of five ODIs, returns to lead the side in South Africa.
The tour comprises six ODIs with the first against Ireland on September 27 followed by five against South Africa beginning on September 30.
Australia - Steve Smith (capt), David Warner, George Bailey, Scott Boland, James Faulkner, Aaron Finch, John Hastings, Travis Head, Mitchell Marsh, Shaun Marsh, Joe Mennie, Chris Tremain, Matthew Wade, Daniel Worrall, Adam Zampa.