The demonstration flight, whose lone occupant is a test dummy named Ripley, is a crucial step in Nasa's delayed quest to resume human space flight from the USA this year. After a five-day mission on the orbital outpost, Crew Dragon was set to autonomously detach about 2:30 a.m EST (0730 GMT) on Friday and descend to earth for an 8:45 a.m. splash-down off Florida's Cape Canaveral coast.
Returning to Earth is described as the toughest part of the mission.
Elon Musk, the CEO of U.S. private aerospace manufacturer SpaceX, called Russia's rocket engineering "excellent" and said the country's rocket engines are the best now flying, also suggesting that the reusable version of Russia's Angara rocket would be "great".
A final abort test is scheduled for June and if that goes well NASA astronauts Bob Behnken and Doug Hurley could fly on the first crewed flight of Crew Dragon in July, according to NASA's most recent timeline.
NASA has awarded SpaceX and Boeing Co $6.8 billion (£5.2 billion) in all to build competing rocket and capsule systems to launch astronauts into orbit from American soil, something not possible since the U.S. Space Shuttle was retired from service in 2011.
The reentry is one of the biggest tests of the Dragon and of SpaceX, the company founded by Musk in 2002 with the ultimate goal of flying humans to Earth's orbit and beyond.
A SpaceX rocket had launched the 16-foot-tall capsule from the Kennedy Space Center in Florida Saturday morning.
But like the launch, the docking went off without a hitch, and soon the three astronauts on board the station - NASA's Anne McClain, Oleg Kononenko of Russian Federation, and Canada's David Saint-Jacques - were able to check out the first commercial space vehicle designed for human space flight ever to dock with the station. He found the capsule "very slick" and called it business class.
The successful landing would be a coup for SpaceX and a relief for Musk, who said he wouldn't be able to relax until the spacecraft had landed safely.
Musk, also co-founder of electric vehicle maker Tesla Inc, will be watching closely.
Musk has also faced trouble at SpaceX. "Reusable version of their new Angara rocket would be great", Musk wrote on Twitter on Thursday.