In doing so, they will become the new faces of American space exploration.
Americans Reid Wiseman, Victor Glover and Christina Koch will make the voyage with their Canadian colleague Jeremy Hansen, and are now preparing to take off as soon as Wednesday.
The journey, set to last around 10 days, will take the astronauts on a loop around the Moon, though they will not land on its surface.
The crew comprises the first woman, the first person of color and the first non-American to take part in such a journey.
Those are key differences from the Apollo era, which included the first and only humans to travel to the Moon.
Here is a closer look at the crew:
- Reid Wiseman -
At 50 years old, Reid Wiseman is the mission's commander.
The native of Baltimore joined NASA in 2009 following a 27-year career in the US Navy.
"I never thought I'd be an astronaut," he said on a NASA podcast. "I mean, come on, it's like an unobtainable dream."
Until it's not: in 2014, Wiseman traveled to space for a 165-day mission aboard the International Space Station, and later served as NASA's chief of the astronaut office.
After losing his wife to cancer in 2020, he raised his two daughters -- now teenagers -- on his own.
In January, he said he aimed for transparency in explaining to them the inherent risks of his career and his coming journey.
"I told them, 'here's where the will is, here's where the trust documents are,'" he said. "And if anything happens to me, here's what's going to happen to you."
"And that's just that is a part of this life."
- Victor Glover -
Another Navy veteran, Victor Glover, 49, will serve as pilot of the Orion spacecraft.
The native of California and father of four daughters was working as a legislative advisor in the US Senate when NASA selected him in 2013.
He has recounted youthful dreaming of becoming a police officer like his father.
But watching a Space Shuttle launch on his family's television set changed his perspective: "I thought, 'I really want to drive one of those.'"
"And yes, I said drive, because I didn't know any pilots or engineers."
He will become the first Black man -- and person of color, period -- to travel to the Moon.
In 2020, he became the first African American to take part on a long-duration mission to the ISS.
He emphasized at the time that the historic first was made possible thanks to those who came before him, paying tribute to figures including Guion Bluford, the first African American to travel to space in 1983.
- Christina Koch -
American astronaut Christina Koch, 47, will become the first woman to take part in a lunar mission.
Like Glover, she was also chosen by NASA in 2013.
Her background is particularly eclectic: an engineer by training, she is a seasoned explorer who has worked in extreme environments including Antarctica.
She long dreamed of becoming an astronaut, she has said, noting the poster of the iconic "Earthrise" image plastered to the wall of her childhood bedroom.
That photograph was taken during the Apollo 8 mission in 1968.
"I always say to people, do what scares you," she says of her personal motto. "And that means I have to follow my own advice."
Koch already holds the record for longest spaceflight by a woman -- 328 days -- and also participated in the first spacewalk performed entirely by women, alongside her colleague Jessica Meir.
- Jeremy Hansen -
Canadian Jeremy Hansen, 50, rounds out the crew and will be the first non-American to fly around the Moon.
Following his career as a fighter pilot in the Royal Canadian Air Force, the Canadian Space Agency brought him into its ranks in 2009.
Post-training he served for several years as a liaison between Earth and the ISS, after which he was entrusted with training a new class of astronauts.
He has said that as a child he found a photograph of Neil Armstrong on the Moon, a moment that sparked his passion for space exploration.
The Artemis 2 mission will be his first journey away from Earth -- and with that, the father of three will fulfill a lifelong dream.
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