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Astronauts Doug Hurley and Bob Behnken have begun their descent to Earth after a two-month stay on the space station.
Their SpaceX Dragon Capsule "Endeavour" has fired its thrusters to drop it out of orbit for a splashdown just south of Pensacola on Florida's Gulf coast.
A successful end to the crew's mission will initiate a new era for the US space agency Nasa.
All its human transport needs just above the Earth will in future be purchased from private companies.
The government agency says contracting out in this way will save it billions of dollars that can be diverted to getting astronauts to the Moon and Mars.
California's SpaceX company is overseeing Hurley's and Behnken's mission. The Dragon capsule is its property.
The vehicle fired its thrusters at 13:56 EDT (18:56 BST; 17:56 GMT), a manoeuvre that committed the conical craft to re-entry - one of the most dangerous phases of spaceflight.
Image copyright NASA Image caption Bob Behnken (L) and Doug Hurley (R) launched to the space station at the end of MayThe high velocity descent through the atmosphere produces a lot of heat that must be diverted away from the vehicle by a forward, protective shield. Parachutes have the final task of lowering the capsule into the water.
Splashdown is expected at 14:48 EDT (19:48 BST; 18:48 GMT). Recovery ships are already in the area awaiting the capsule's return.
It's now 45 years since the last US crewed capsule made a water landing. That was an Apollo vehicle which returned to the Pacific after meeting up with a Soviet Soyuz craft above the Earth.
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Doug Hurley said he'd read the reports from the time and discovered that astronauts could experience some nausea when bobbing about on the water waiting for recovery.
"There are bags if you need them, and we'll have those handy," he told reporters on Friday. "We'll probably have some towels handy as well. If that needs to happen, it certainly wouldn't be the first time. Folks that fly in space know that sometimes going uphill can have an effect on your system and sometimes coming downhill is the same way."
Image copyright NASA Image caption Nasa and SpaceX practised the splashdown procedures in an uncrewed mission last yearThe astronauts' Dragon ship launched to the space station at the end of May on a Falcon 9 rocket, also supplied by SpaceX.
Their mission has served as an end-to-end demonstration of the astronaut "taxi service" the company, owned by tech entrepreneur Elon Musk, will be selling to Nasa.
The Boeing corporation is also developing a crew capsule solution but has had to delay its introduction after encountering software problems on its Starliner capsule.
Assuming this demonstration mission is completed successfully with a copybook splashdown, Nasa will move forward with routine, "operational" SpaceX flights, perhaps as early as the end of September.
Endeavour will go for refurbishment with the expectation it be put back on a rocket next year.
The crew for this flight, by chance, will include astronaut Megan McArthur, the wife of Bob Behnken.
The husband said he would have some tips on where best to pack personal items in the capsule. "Just like on any trip, if you pack things appropriately, it can be fun," he joked.
"But if you pack everything at the bottom of the big van that you take on vacation, and you've got to get it all out one item at a time at various times, it can be tiring and eat into your enjoyment."
Hurley and Behnken are bringing back a commemorative US flag that was left on the space station by the crew of the last shuttle mission (which happened to include Doug Hurley). The Stars and Stripes also flew on the very first shuttle mission in 1981. It's expected to go back into space again when America returns astronauts to the Moon later this decade.
Jonathan.Amos-INTERNET@bbc.co.uk and follow me on Twitter: @BBCAmos
