Axiom Mission 4, or Ax-4, launched from NASA's Kennedy Space Center in Florida at 2:31 am (0631 GMT), with a brand-new SpaceX Crew Dragon capsule riding atop a Falcon 9 rocket.
The vehicle is scheduled to dock with the orbital lab on Thursday at approximately 1100 GMT and remain there for up to 14 days.
Aboard the spacecraft were pilot Shubhanshu Shukla of India; mission specialists Slawosz Uznanski-Wisniewski of Poland and Tibor Kapu of Hungary; and commander Peggy Whitson of the United States, a former NASA astronaut who now works for the company Axiom Space, which organizes private spaceflights, among other things.
The last time India, Poland or Hungary sent people to space, their current crop of astronauts had not yet been born -- and back then they were called cosmonauts, as they all flew on Soviet missions before the fall of the Iron Curtain.
Shukla became the first Indian in space since Rakesh Sharma, an air force pilot who traveled to the Salyut 7 space station in 1984 as part of a Soviet-led initiative to help allied countries access space.
India's space agency, ISRO, sees this flight as a key stepping stone toward its own maiden crewed mission, planned for 2027 under the Gaganyaan program, meaning "sky craft" in Hindi.
Indian Prime Minister Narendra Modi hailed the successful launch of the Ax-4 space mission.
"He (Shukla) carries with him the wishes, hopes and aspirations of 1.4 billion Indians. Wish him and other astronauts all the success!" he wrote on X.
While aboard the ISS, Shukla is widely speculated to speak with Modi -- in a soft-power moment aimed at stoking national pride.
All three countries are footing the bill for their astronauts. Hungary announced in 2022 it was paying $100 million for its seat, according to spacenews.com. India and Poland have not disclosed how much they are spending.
"We've got this! Poland has reached for the stars," Polish Prime Minister Donald Tusk said on X, alongside a video himself watching the launch on a screen at the Copernicus Science Centre in Warsaw.
"Who knows how many future Polish astronauts watched Slawosz's launch with me? Everyone was very excited and very proud," Tusk said in another post, which included a photo of him seated next to several children at the science centre.
- Space spat -
The Ax-4 launch comes after multiple issues delayed the mission, originally slated for early June.
It also follows an explosive online spat between US President Donald Trump and SpaceX chief Elon Musk, the world's richest person and, until recently, Trump's ally and advisor.
Trump threatened to yank SpaceX's federal contracts -- worth tens of billions of dollars -- prompting Musk to threaten an early retirement of Dragon, the only US spacecraft currently certified to carry astronauts to the ISS.
Musk walked back the threat a few hours later and in the days that followed, sought to distance himself further, writing on X that he had gone "too far."
Any rupture between SpaceX and the US government would be massively disruptive, given NASA and the Pentagon's reliance on Falcon 9 and Falcon Heavy to send up crew, cargo, satellites and probes.
But for now, analysts believe both sides are too entangled to risk a serious break.
The Ax-4 flight marks the debut of the fifth and final Crew Dragon vehicle, which will be named once it reaches orbit, joining Endeavour, Resilience, Endurance and Freedom in the active fleet.
SpaceX ultimately plans to phase out its current vehicles in the 2030s in favor of Starship, its giant next-generation rocket currently in development.
Ax-4 will carry out around 60 experiments, including studies on microalgae, sprouting salad seeds, and how well microscopic creatures called tardigrades survive in space.
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