The capsule rocketed into orbit to fetch the test pilots whose Boeing spacecraft returned to earth empty earlier this month because of safety concerns.
The switch in rides left it to NASA's Nick Hague and Russia's Alexander Gorbunov to retrieve Butch Wilmore and Suni Williams.
Since NASA rotates space station crews approximately every six months, this newly launched flight with two empty seats reserved for Wilmore and Williams will not return until late February.
Officials said there was not a way to bring them back earlier on SpaceX without interrupting other scheduled missions.
LIVE: Our — NASA (@NASA) @SpaceX #Crew9 mission launches to the @Space_Station. Liftoff from Cape Canaveral Space Force Station is scheduled for 1:17pm ET (1717 UTC). Questions? Use #AskNASA https://t.co/ShUyD36syYSeptember 28, 2024
By the time they return, the pair will have logged more than eight months in space.
They expected to be gone just a week when they signed up for Boeing's first astronaut flight that launched in June.
NASA ultimately decided that Boeing's Starliner was too risky after a cascade of thruster troubles and helium leaks marred its trip to the orbiting complex.
The space agency cut two astronauts from this SpaceX launch to make room on the return leg for Wilmore and Williams.
Williams has since been promoted to commander of the space station, which will soon be back to its normal population of seven.
Once Hague and Gorbunov arrive this weekend, four astronauts living there since March can leave in their own SpaceX capsule.
Their homecoming was delayed a month by Starliner's turmoil.
Hague noted before the flight that change is the one constant in human spaceflight.
"There's always something that is changing. Maybe this time it's been a little more visible to the public," he said.
Hague was thrust into the commander's job for the rescue mission based on his experience and handling of a launch emergency six years ago.
The Russian rocket failed shortly after lift-off, and the capsule carrying him and a cosmonaut catapulted off the top to safety.
Rookie NASA astronaut Zena Cardman and veteran space flier Stephanie Wilson were pulled from this flight after NASA opted to go with SpaceX to bring the stuck astronauts home.
The space agency said both would be eligible to fly on future missions.
Gorbunov remained under an exchange agreement between NASA and the Russian Space Agency.
"I don't know exactly when my launch to space will be but I know that I will get there," Cardman said from NASA's Kennedy Space Center, where she took part in the launch livestream.
Wilson joined her there for the early afternoon lift-off.
Moments before liftoff, Hague paid tribute to his two colleagues left behind: "Unbreakable. We did it together".
Once in orbit, he called it a "sweet ride" and thanked everyone who made it possible.
SpaceX has long been the leader in NASA's commercial crew program, established as the space shuttles were retiring more than a decade ago.
SpaceX beat Boeing in delivering astronauts to the space station in 2020 and it is now up to 10 crew flights for NASA.
Boeing has struggled with a variety of issues over the years, repeating a Starliner test flight with no one on board after the first one veered off course.
The Starliner that left Wilmore and Williams in space landed without any issues in the New Mexico desert on September 6, and has since returned to Kennedy Space Center.
15°C