"Let me be clear - the United States is a Pacific nation. We care deeply about what happens here, and we're here to stay," Mr Pompeo told reporters.
"We think of this as an unbreakable relationship - grounded in our shared values of democracy, the rule of law and human rights."
The US and Australia wanted to help countries prosper through trade and investment, Mr Pompeo said, rather than "zero-sum deals where one wins and the other risks losing" - a clear swipe at strategic rivals China.
He also lauded the Morrison government's "Pacific step-up", as well as a shared concern for strategic tension in the South China Sea, where China has established and militarised atolls and reefs.
"We're both concerned about China's militarisation of the South China Sea, both keeping an eye on investment that mires our friends in debt," Mr Pompeo said.
Dr Esper has previously accused China and Russia of seeking to displace the US and "shift the balance of power in their favour" and told US reporters that the world had returned to "an era of great power competition".
Senator Payne congratulated Dr Esper for his recent appointment to the Defense portfolio and said the countries' vision for the region was shared.
"It's important to reinforce that without strong US engagement, the region that we all want, the region we need, can't be achieved," Senator Payne said.
"That's a region in which all states are respected, regardless of size or power."
Mr Pompeo will address a Centre for Independent Studies forum with Senator Payne on Sunday afternoon, before heading to Micronesia on Monday.