Trade, climate and the digital economy are expected to be key topics for Anthony Albanese at the APEC summit in San Francisco being hosted by US President Joe Biden.
The prime minister left Canberra on Wednesday to head to the Asia-Pacific Economic Co-operation leaders' meeting.
The theme of the summit is "Creating a Resilient and Sustainable Future for All".
"Engagement with APEC partners is critical for seizing the opportunities to create the jobs of the future, to expand our economic growth, and to take advantage of our location - on the doorstep of the fastest growing region in human history," Mr Albanese said in a statement on Wednesday.
Free and open rules-based trade, supply chain resilience and sustainable and inclusive economic growth would be Australia's priorities, he said.
One of the most closely watched aspects of the summit will be Mr Biden's meeting with Chinese President Xi Jinping, their second in-person since the US president took office in January 2021.
The two leaders are expected to discuss what the White House described as "advancing the ball" on military-to-military communications with China, as well as the Israel-Hamas war and Russia's invasion of Ukraine.
Mr Albanese told parliament on Wednesday he would be making the point to other leaders that "democratic nations must stand up consistent with the international rule of law".
The prime minister recently noted the Chinese president's participation in APEC and said talks with Mr Biden would be important.
"What we need to do is to have more dialogue and discussion because out of that comes greater understanding and it can also avoid mistakes."
The visit is expected to include a meeting with Microsoft chairman and CEO Satya Nadella who in October announced a $5 billion investment in cloud computing and artificial intelligence infrastructure in Australia, as well as training and cybersecurity programs.
This year marks 30 years since US president Bill Clinton hosted the first APEC leaders' meeting, at Blake Island, Washington.
Mr Clinton also began the colourful tradition of providing the leaders with themed clothing, handing out bomber jackets to his visiting counterparts.
The 21 APEC member economies account for nearly 40 per cent of the global population, almost half of global trade, and 60 per cent of global GDP.
The leaders will discuss trade and investment, the digital economy, health, gender equity and equality, clean energy and climate, anti-corruption and food security.
Opposition Leader Peter Dutton called on Mr Albanese to cancel his trip to deal with pressing domestic issues.
Mr Dutton said the prime minister should instead convene a meeting with premiers and chief ministers to discuss growing anti-Semitism and civil unrest in Australia, amid the escalating conflict in Gaza.
The Liberal leader also called for Mr Albanese to address security concerns in the wake of criminals being released into the community following a High Court decision on immigration detention.
The US is pressing for APEC-wide action on mitigating emissions in the transport sector, including cleaner fuels in the aviation and maritime industries, and leading the world on adopting zero-emissions vehicles.
Leaders are also expected to discuss progress on the 14-nation Indo-Pacific Economic Framework, which involves Australia.
The IPEF covers four pillars of work: trade, supply chains, clean energy and tax.
APEC's members are: Australia, Brunei, Canada, Chile, China, Hong Kong, Indonesia, Japan, South Korea, Malaysia, Mexico, New Zealand, Papua New Guinea, Peru, the Philippines, Russia, Singapore, Taiwan, Thailand, the United States and Vietnam.
Australian Associated Press