Anthony Albanese's trip to Washington comes at a time of heightened security tensions across the globe and challenging conditions for the Australian economy.
The official visit next week is expected to include a state dinner at the White House with a host of celebrity guests and a bilateral meeting with US President Joe Biden.
The prime minister and president were due to meet in Sydney in May, with a side trip by the US leader to address parliament in Canberra, but domestic political pressures kept Mr Biden from travelling.
While the conflict in Ukraine, Israel's war with Hamas and China's muscle-flexing in the region will be on the agenda, the two leaders will seek to focus at least part of the week on climate change and innovation.
It will be the ninth meeting between the two leaders since Labor's election win in 2022.
The Labor leader told parliament this week the US alliance was the "central pillar" of Australia's foreign policy.
"Our nations are united by our common values, our deep history and our shared vision," Mr Albanese said.
"But this visit, of course will be focused on building an alliance for the future."
The Australian diplomatic delegation will be keen to get some insight into progress on the US Congress easing the rules on defence technology sharing with Britain and Australia.
The future of the multi-billion-dollar nuclear-powered submarines program hinges on Congressional approval, but a number of lawmakers are concerned about the potential impact on timeframes for domestic defence manufacturing in the US.
The Albanese government has been talking up its defence spending following a major review, committing to bolster it by an additional 0.2 per cent of GDP above its existing trajectory by the end of the decade.
This will include more than $19 billion over the next four years to acquire long-range strike systems, manufacture guided munitions, and upgrade critical air bases across northern Australia, working with the US and UK.
The leaders are expected to discuss Russia's invasion of Ukraine, with Australia so far committing almost $1 billion in defence support.
Gaining insight into the potential for US-China conflict over Taiwan will also be of interest for Australia's delegation.
Australia does not take a position on the final status of Taiwan other than it must be arrived at peacefully, consistent with the will of peoples on both sides of the Strait and not though the use of force or coercion.
The government also supports ASEAN’s code of conduct negotiations with China regarding maritime boundary disputes in the South China Sea.
The White House said the visit would "underscore the deep and enduring alliance between the United States and Australia and the two nations’ shared commitment to supporting an open, stable and prosperous Indo-Pacific".
The Assange family is hoping the prime minister will raise the issue of Julian Assange's release, noting Mr Albanese's expression of frustration about the lack of a diplomatic solution.
One of Mr Albanese's aims on the trip will be to draw a link between trade, the green economy, education and Australian jobs.
The two countries in May signed a compact on critical minerals and clean energy.
It's expected further cooperation could be pledged on innovation and technology, which is considered the key driver of economic growth for the US and Australia.
Mr Albanese will also meet with Vice President Kamala Harris, Secretary of State Antony Blinken and Secretary of Defence Lloyd Austin, and attend the opening of Australia's new embassy.
The chancery itself is seen as a model of Australian innovation, featuring a "green roof" with an extensive photovoltaic array.