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Mitchell and Samo missed the June tests, when Australia was upset by Scotland before clean sweeping Wales 3-0, but finished the Super Rugby season well, before impressing at the recent national training camps.
Mitchell returns from ankle and hamstring injuries. Only five players have scored more tries in tests for the Wallabies than the 28-year-old, who appeared in his 58th and most recent test for Australia during the World Cup last year in New Zealand.
Samo is back from a shoulder injury. The widely-travelled loose forward made a remarkable test return in 2011 after a seven-year absence and ended the year with a Tri Nations title.
Three uncapped players named today include two of the most recent Australian under-20 captains - Liam Gill, who skippered the side at this year's World Cup in South Africa, and his predecessor Jake Schatz.
Hard-working NSW Waratahs lock Kane Douglas also earns a call-up.
The inclusion of Gill, plus June newcomer Michael Hooper from the Brumbies, bolsters the Wallabies' back-up resources behind premier openside flanker and captain, David Pocock.
The selections of 122kg second-rower Douglas and Sitaleki Timani (120kg) add size and power to the Australian set-piece.
The two young locks, along with Rob Simmons, will be mentored by test centurion Nathan Sharpe. The 34-year-old's decision to stay on for the Rugby Championship provides an opportunity to chase down George Smith as the second most-capped Wallaby.
The Rugby Championship, which introduces Argentina to the annual southern hemisphere competition for the first time, will run over six weekends from August 18 to October 6.
Australia won the final Tri-Nations last year, a decade after the Wallabies had won the second of their three tournament titles in 2001.
Several injured players were unavailable for the 30-man squad but will come back into contention during the tournament once they complete rehabilitation.
Ben Alexander, Adam Ashley-Cooper, Berrick Barnes, Kurtley Beale, Quade Cooper, Dave Dennis, Kane Douglas, Anthony Faingaa, Saia Faingaa, Will Genia, Liam Gill, Mike Harris, Scott Higginbotham, Michael Hooper, Rob Horne, Digby Ioane, Sekope Kepu, Drew Mitchell, Stephen Moore, Nick Phipps, David Pocock (capt), Tatafu Polota-Nau, Benn Robinson, Radike Samo, Jake Schatz, Nathan Sharpe, Rob Simmons, James Slipper, Sitaleki Timani, Nic White