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4 year oldThe crew rode to orbit in a rocket and capsule provided by the SpaceX company.
It's only the second time the firm has supplied the service.
The US space agency Nasa has said it is now entering a new era in which routine astronaut journeys to low-Earth orbit are being conducted by commercial providers.
The four individuals making their way up to the ISS are the Americans Michael Hopkins, Victor Glover and Shannon Walker, and the highly experienced Japanese space agency (Jaxa) astronaut Soichi Noguchi.
By participating in this mission, Noguchi becomes only the third person in history to leave Earth in three different types of space vehicle, having previously flown on Soyuz and shuttle hardware.
The crew's Falcon rocket and Dragon capsule left the pad at the Kennedy Space Center at 19:27 local time (00:27 GMT, Monday).
It took 12 minutes for the Falcon to get the Dragon into the right part of the sky and drop it off.
"Well done, that was one heck of a ride," crew commander Mike Hopkins radioed down to controllers. "Congratulations to everyone. Resilience is in orbit."
"Resilience" is the name the astronauts have given their capsule.
The ship will use its own thrusters to complete the rest of the journey up to the station. A docking with the orbiting platform is set for about 0400 GMT on Tuesday.
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