America's first crewed spaceship since the Space Shuttle era was set to splash down in the Gulf of Mexico on Sunday.
Astronauts Bob Behnken and Doug Hurley were carrying out final preparations in the SpaceX Crew Dragon capsule "Endeavour" which should land off the coast of Pensacola at 2:48 pm (1848 GMT).
A successful mission would demonstrate that the United States once again has the capacity to send its astronauts to space and bring them back.
The US has had to rely on Russia for this purpose since the last Space Shuttle flew in 2011.
NASA footage showed the recovery boat "GO Navigator," making its way to the site of the first water landing for a US spaceship since the 1975 joint Apollo-Soyuz mission.
Tropical Storm Isaias, which had scuppered Endeavour's original landing site in the Atlantic, was nearing Florida's east coast Sunday morning, hundreds of miles away.
The mission is also a major win for Elon Musk's SpaceX, which was founded in only 2002 but has leap-frogged its way past Boeing, its main competitor in the commercial space race.
The US has paid the two companies a total of about $7 billion for their "space taxi" contracts, though aerospace giant Boeing's efforts have badly floundered.
- Atmospheric re-entry -
Over the coming hours, the Crew Dragon capsule will have to perform several precise procedures in order to return home safely.
At 1:51 pm (1751 GMT), the ship will jettison its "trunk" that contains its power, heat and other systems, which will re-enter the Earth's atmosphere and burn up.
Endeavour will then fire its thrusters to maneuver itself into the proper orbit and trajectory for splashdown.
At 2:32 pm (1832 GMT) it will re-enter the atmosphere at a speed of around 17,500 mph (28,000 kph).
The ship's heat shield will need to withstand temperatures of 3,500 degrees Fahrenheit (1900 degrees Celsius), conditions which will in turn cause a communications blackout for several minutes.
Endeavour will then deploy two sets of parachutes on its descent, bringing its speed down to a mere 15 mph (24 kph) as it hits the water.
The two astronauts will be brought on board a recovery ship for a medical checkup before being taken ashore.
- Astro dads -
The SpaceX Crew Dragon spacecraft set out off from the International Space Station Saturday evening.
Footage showed the capsule drifting slowly away from the ISS in the darkness of space, ending a two month stay for the crewmates.
"And they are off!" NASA tweeted, with Doug Hurley and Bob Behnken set to splash down Sunday.
During a farewell ceremony on the station, Behnken said that "the hardest part was getting us launched. But the most important part is bringing us home."
Addressing his son and Hurley's son, he held up a toy dinosaur that the children chose to send on the mission and said: "Tremor The Apatosaurus is headed home soon and he'll be with your dads."
Behnken and Hurley's return marks only the beginning for the Crew Dragon as SpaceX and NASA look ahead to future missions.
Endeavor will be brought back to the SpaceX Dragon Lair in Florida where it will undergo a six-weeks-long inspection process, as teams pore over its data and performance in order to certify the vessel as worthy of future low-Earth orbit missions.
The next mission -- dubbed "Crew-1" -- will involve a four member team: commander Michael Hopkins, pilot Victor Glover, and mission specialist Shannon Walker of NASA, along with Japan Aerospace Exploration Agency mission specialist Soichi Noguchi.
Take-off is set for late September and the crew are due to spend six months on the space station.