Hillary Clinton says WA is at the centre of a regional "strategic shift" as local energy supplies and trade routes become more important to the world economy.
In her first public event in Perth, the world's most powerful woman underlined America's historic ties with WA and said the US would stay a major player in the region.
Mrs Clinton also talked up Australia's relationship with India and said the US was keen to support the "peaceful rise of China".
Amid tight security, Mrs Clinton gave her address at the launch of the US-Asia studies centre at the University of WA last night.
She acknowledged the billions of dollars of US investment in WA oil and gas and the strategic implications of that growth. "Increasingly these waters are at the heart of the global economy," she said.
She was also keen for Australia to forge closer naval ties with India through joint exercises.
But Mrs Clinton was more cautious on China, saying the US wanted Beijing to be a responsible stakeholder in the world and to open its society and political system.
Mrs Clinton arrived in Perth in her private US Air Force jet under tight security as helicopters and a small army of uniformed and suited security officers invaded the city. She was greeted by Premier Colin Barnett, Ambassador to the US Kim Beazley and Defence Minister Stephen Smith.
With no time to linger, she was ushered to an armoured limousine and her motorcade of 11 vehicles sped to a heavily guarded hotel.
Unlike CHOGM last year, police did not close all nearby roads for the convoy but orchestrated "green corridors" - stopping traffic as the motorcade passed.