Clinton will be joined by Defense Secretary Leon Panetta for the talks with counterparts Bob Carr and Stephen Smith on Wednesday expected to focus on regional security and greater US use of Australian facilities.
It comes after the arrival of US Marine and Air Force units to northern Australia, seen as evidence of an American "re-balance" towards the Pacific after a decade of ground wars in Iraq and Afghanistan.
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"We're going to deal with the suite of strategic issues that are of importance to us," Smith said ahead of Clinton's arrival.
It is expected to be her last official trip Down Under with America's top diplomat saying she plans to step down at the end of her four-year term in January despite President Barack Obama's re-election.
The much-travelled US diplomat then heads to Singapore on Friday before joining up with Obama in Thailand on his first foreign visit since he won a second term.
She is then scheduled to accompany Obama on a landmark trip to Myanmar on November 19, before heading with him to Cambodia for the ASEAN (Association of Southeast Asian Nations)-US leaders meeting and the East Asia summit.
