The crew will ride to orbit in a Dragon capsule atop a Falcon-9 rocket. It will be only the second time that this launch system has been used to transport people.
It follows a successful demo flight conducted back in May, which marked the resumption of astronaut missions from US soil after a gap of nine years.
The Falcon-Dragon combo is due to depart the Kennedy Space Center in Florida at 19:27 local time (00:27 GMT, Monday).
It's an "instantaneous launch window", meaning the mission must leave on the button if it wants to catch the station as it circles the Earth overhead.
Much depends on the weather, of course. Unacceptable winds on the space coast have already forced one 24-hour delay.
Should there be a further postponement for any reason, the next attempt would be made on Wednesday.
The crew comprises three US space agency (Nasa) astronauts - Commander Michael Hopkins, Victor Glover and Shannon Walker - and the highly experienced Japanese space agency (Jaxa) astronaut Soichi Noguchi.
They've named their Dragon ship "Resilience".
The group will spend roughly six months on the station, raising its complement to seven.
Nasa's Kate Rubins and the Russian space agency (Roscosmos) cosmonauts Sergey Ryzhikov and Sergey Kud-Sverchkov are already aboard the 410km-high platform. Having a seven-strong team on the ISS will triple the amount of microgravity science that can be conducted on the platform.
Victor Glover will become the first African-American astronaut to undertake a long-duration mission on the station. In the 20 years that humans have permanently occupied the orbiting facility, black astronauts have only ever visited for short periods.
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