Batsmen Matt Renshaw and Nic Maddinson are among six selection changes in a brutal shake-up of Australia's Test team.
Renshaw, Maddinson, South Australian paceman Chadd Sayers and Victorian batsman Peter Handscomb could all make Test debuts against South Africa in Adelaide from Thursday.
Matthew Wade and Jackson Bird are also recalled - Joe Burns, Callum Ferguson, Adam Voges, Peter Nevill and Joe Mennie all axed after the second Test loss in Hobart.
Australia hasn't given debuts to four players in one Test since 1978.
But in a stunning carve-up after Rod Marsh quit as chairman of selectors last week, selectors led by interim chairman Trevor Hohns made drastic changes.
Burns was dumped after one Test back as David Warner's opening partner, with 20-year-old Queenslander Renshaw favoured.
South Australia's Ferguson and Mennie were unceremoniously axed after both failed on Test debut in Hobart.
And gloveman Nevill has been dropped for Wade, a better batsman.
Sayers, an accurate swing bowler who has consistently revelled on home turf in Adelaide, will vie with Tasmanian quick Jackson Bird to replace Mennie.
Handscomb, 25, and Maddinson, 24, are set for debuts in the middle-order.
Hohns said Renshaw had "established himself in a short period of time as one of the best young opening bats in the country".
"His form is currently very good and we see him as a very exciting prospect for the future," Hohns said in a statement.
"Peter's form over the last couple seasons, and with Australia A, has been very consistent. He has a good all-round game and we think he is the type of player who could succeed at the next level.
"Nic is an exciting and talented young player and we feel now is the ideal time for him to be involved with the Australian team. He has the ability to break the game open and we think he will flourish in this environment."
Squad: Steve Smith (capt), David Warner, Jackson Bird, Peter Handscomb, Josh Hazlewood, Usman Khawaja, Nic Maddinson, Nathan Lyon, Matt Renshaw, Chadd Sayers, Mitchell Starc, Matthew Wade (12th man to be named).