Nasa has launched astronauts into space from US soil for the first time in nine years, with Doug Hurley and Bob Behnken on board SpaceX's Dragon capsule and Falcon 9 rocket.
The Falcon 9 booster landed safely upright on the droneship called Of Course I Still Love You, Space X said.
The duo were due to lift off on Wednesday, but the mission was aborted less than 17 minutes before launch time over concerns that the event could trigger lightning.
Since ending its Space Shuttle programme in 2011, Nasa has depended on Russia's space agency Roscosmos to transport its astronauts to the space station.
In 2014, Nasa awarded SpaceX and Boeing contracts to provide crewed launch services to the space station as part of its Commercial Crew Programme.
According to Nasa, the aim of the Demo-2 mission is to show SpaceX's ability to ferry astronauts to the space station and back safely.
It is the final major step required by SpaceX's astronaut carrier, the Crew Dragon, to get certified by Nasa's Commercial Crew Programme for more long-term manned missions to space.
SpaceX's Falcon 9 rocket will take off from the Launch Complex 39A at the Kennedy Space Centre in Florida, carrying the Crew Dragon spacecraft where Mr Behnken, 49, and Mr Hurley, 53, will be strapped in.
Mr Behnken will serve as the mission's joint operations commander and take responsibility for the rendezvous, docking and undocking of the Dragon capsule, while Mr Hurley will be in charge of the launch, landing and recovery of the vehicle in his role as the Crew Dragon spacecraft commander.
Mr Behnken and Mr Hurley will join the three other space station residents – Nasa's Chris Cassidy and Russia's Anatoli Ivanishin and Ivan Vagner – to become members of the Expedition 63 crew.
Mr Vagner tweeted earlier to say he was waiting for the duo at the space station.
The mission is expected to last anything between one and four months, with a number of tests being performed on the Crew Dragon.