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The first journey to deep space since 1972 comes at a crucial time in Donald Trump's presidency.
The US is bitterly divided on topics ranging from the ongoing US strikes in Iran to immigration and the economy.
So a successful Artemis mission, sending four astronauts to the Moon on Wednesday, could give Trump's administration a boost. The potential benefits are huge - a competitive edge with China, the possibility of a lunar gold rush, and a rare moment of national unity.
Officially, the mission - which will take the crew further into space than anyone has ever been before - is a stepping stone, Nasa says, towards a permanent lunar base and eventually, Mars.
While US interest in returning to the Moon pre-dates his entry into politics, Trump directly created what became Artemis in his first term, vowing to "launch American astronauts to plant the Stars and Stripes on the planet Mars". He also saw military opportunities and launched a new arm of the Pentagon, Space Force.
In his second term, however, Trump's goal has shifted to the Moon. In December last year, he signed an executive order calling for a US return to the Moon by 2028 and the establishment of a permanent outpost there by 2030. The order said that US superiority in space was a measure of national vision and willpower, contributing to the nation's strength, security and prosperity.
Three Americans and one Canadian head to the Moon on Wednesday
Not mentioned in the executive order was lunar competition from China - a factor that Nasa administrator Jared Isaacman has laid out explicitly.
"We find ourselves with a real geopolitical rival, challenging American leadership in the high ground of space," Isaacman said at a Nasa event on 24 March. "This time, the goal is not flags and footprints," he added. "This time, the goal is to stay. America will never again give up the Moon."
During the Cold War space race with the Soviets, the point of getting to the Moon was almost entirely geopolitical.
With Washington and Moscow locked in a battle for ideological influence on Earth, space became another arena in which to demonstrate technological superiority, which for the US became increasingly urgent after the 1957 Soviet launch of Sputnik - the world's first satellite - sent shockwaves through the US.
The 1957 Soviet launch of Sputnik - the world's first satellite - was a wake-up call for the US
John F Kennedy made the mission explicitly political, both publicly and in private.
"This is important for political reasons," Kennedy said in a declassified 1962 recorded White House conversation with Nasa administrator James Webb. "This is, whether we like it or not, a race."
The new Moon race is between the US and China, which has its own fast-moving plans to put a crew on the lunar surface in the next few years.
This exploration could have a vast, potentially lucrative economic angle at a time when both countries are locked in trade tensions.
Former Nasa administrator Sean O' Keefe told the BBC that the nations that land on the Moon will have the advantage of exploring and developing the resources that are there.
"After all these years of thinking it was nothing more than a dust bowl, we have come to realise it has a significant amount of helium 3," he said, adding that the element can be potentially used to operate small, compact nuclear fusion reactors with relatively long lifespans. "That opens up all sorts of other opportunities."
Additionally, the moon is home to water ice, which can be used for rocket propulsion, as well as rare earth minerals such as lithium, platinum and other materials critical to electronics and clean energy technology.
On Earth, these markets are currently dominated by Chinese mining operations, a key concern of the Trump administration.
The value of these resources remains unknown, but could be massive. Helium 3 alone currently trades at more than $20,000 per kilogram, making it one of the most valuable resources on earth.
Clayton Swope, a veteran of the CIA's Directorate of Science and Technology and former adviser on space affairs on Capitol Hill, compared the "lunar gold rush" to the Lewis and Clark expedition across the western US in the early 1800s.
"We didn't quite know the value of the western part of the US, or the Pacific Northwest, but we thought it was there," he said. "Part of [the mission] is trying to figure out what that value is. We can't quite put a price tag or a dollar amount on the Moon, but you can't get away from that competition and rivalry with China."
The White House certainly views space as another arena for the US to exert its dominance.
"With President Trump's America-First policies, the United States will lead humanity into space and enter a new era of groundbreaking achievements in space technology and exploration," said spokeswoman Liz Huston.
Trump's generation grew up with images of astronaut Neil Armstrong taking his historic first steps on the moon in July 1969 - they are etched on their collective consciousness.
Trump's generation grew up with images of astronaut Neil Armstrong taking his historic first steps on the moon in July 1969
At the time, the US was in turmoil.
American soldiers were fighting and dying in an unpopular war in Vietnam; civil rights tensions were rife; the assassinations of Martin Luther King and Robert Kennedy were still being felt; and the polarising figure of Richard Nixon was sat in the White House.
Despite those divisions, an estimated 125 to 150 million Americans tuned in to watch the Apollo 11 Moon landing, providing a rare moment of collective national pride at a difficult time in US history.
Some experts say that the Artemis mission could replicate that again in 2026, at a time when Americans are polarised once more, and again the US is at war.
"Space is one of the few areas that Americans with different political views can enjoy and watch together," said Esther Brimmer, a senior fellow at the Council of Foreign Relations who specialises in space policy.
"The space programme is something that most Americans have grown up with and see as a point of pride," she added. "It's by and large unifying, in terms of the social impact."
"The space programme is something that most Americans have grown up with and see as a point of pride," says Esther Brimmer, a senior fellow at the Council of Foreign Relations
Astrophysicist David Gerdes was five years old when Armstrong walked on the moon.
"One of my very earliest memories was being allowed to stay up way past my usual bedtime, dozing on a blanket in front of our black-and-white television, watching Walter Cronkite report on the Apollo 11 landing," said Gerdes, now a professor at Case Western Reserve University in Ohio.
"Many, many people of all ages were inspired by the technology, the boldness, and the spirit of the astronauts."
For a moment, he adds, it transcended partisan divisions.
"I would certainly hope that a return to the Moon by a group of Americans that is more diverse than those who took part in the 1960s can really help bring the country together."
