Four astronauts left the International Space Station on Monday and were bound for Earth following a more than six month mission.
Led by American astronaut Jasmin Moghbeli, NASA's Crew-7 arrived at the research platform last August aboard a SpaceX Crew Dragon.
The same spacecraft undocked on Monday morning, with Andreas Mogensen of Denmark, Satoshi Furukawa of Japan, and Russian cosmonaut Konstantin Borisov also on board.
Moghbeli, who was making her first spaceflight, paid tribute to the post-Cold War international partnership that paved the way for the construction of the ISS in the 1990s.
"It's an indication of what we can do when we work together," she said during a farewell ceremony on Sunday.
"To think back to when this was just a dream itself, and the people that had the vision, the grit and the courage to pursue this orbiting laboratory in low Earth orbit, I'm really proud to be a part of this."
NASA and SpaceX are targeting as soon as 5:35 am Tuesday (0935 GMT) for a splashdown off the Florida coast.
Space remains a rare area of cooperation between the United States and Russia despite the invasion of Ukraine and Russian President Vladimir Putin's ambitions to reshape the global balance of power. Americans also continue to fly aboard Russian Soyuz rockets that launch from Kazakhstan.
The members of Crew-7 carried out science experiments including collecting samples during a spacewalk to determine whether the station releases microorganisms through life support system vents. Another assessed how microgravity, which accelerates aging, affects liver regeneration.
Crew-7 is the seventh routine NASA mission to the orbital platform for Elon Musk's SpaceX, with the first coming in 2020. The latest, Crew-8, launched on March 4.
NASA pays SpaceX for the taxi service as part of a US program put in place to reduce dependency on Russian rockets following the retirement of the Space Shuttle in 2011.
Boeing is the other contracted private partner, but its program has fallen behind, and now plans to fly its first crew in May.
The first segment of the ISS was launched in 1998, and it has been continuously inhabited by an international crew since 2001.
Its operations are set to continue until at least 2030, after which it will be decommissioned and crash into the ocean. Several private companies are working on commercial space stations to replace it, while China has already established its own orbital lab.