'Everything is proceeding as expected," a NASA official said as the undocking was broadcast.
The spacecraft is carrying NASA astronauts Bob Hines, Kjell Lindgren and Jessica Watkins and European Space Agency astronaut Samantha Cristoforetti back to earth after completing their nearly six month science mission on the ISS.
The departure was originally scheduled for Thursday but was delayed because of high winds over the two potential splashdown areas off the east and west coasts of the US state of Florida, NASA said.
Splashdown is now scheduled to be in one of those two areas just before 5:00 p.m. EDT on Friday afternoon, NASA added.