Paceman Lonwabo Tsotsobe and batsman Vaughn van Jaarsveld will make their South Africa debuts on Sunday in the first Twenty20 game against Australia.
Herschelle Gibbs is recalled but there is no place for Hashim Amla, Neil McKenzie or Morne Morkel in Melbourne.
Australia have added Luke Ronchi to their squad as a late replacement for rested wicketkeeper Brad Haddin.
Also included is batsman David Warner, who has shone in one-day matches but has yet to make his first-class debut.
Cricket Australia announced on Saturday morning that Haddin, 31, was being rested in order to manage his "heavy workload".
606: DEBATERonchi, 27, has played four one-day internationals and hit 36 in his sole Australian Twenty20 appearance.
Selector Andrew Hilditch said he had been given a "deserved opportunity".
Australia (from): Ricky Ponting (capt), Michael Hussey (vc), David Hussey, Ben Hilfenhaus, James Hopes, Nathan Bracken, Brad Haddin, Shaun Marsh, Shaun Tait, David Warner, Ryan Harris, Cameron White, Nathan Hauritz.
South Africa: Herschelle Gibbs, Jacques Kallis, AB de Villiers, JP Duminy, Vaughn van Jaarsveld, Mark Boucher (wk), Albie Morkel, Johan Botha (capt), Dale Steyn, Makhaya Ntini, Lonwabo Tsostobe.
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