The Boeing company is going to launch a test capsule to the International Space Station (ISS).
Known as Starliner, the vehicle will be flying uncrewed on this occasion.
But if it performs without incident, astronauts will start using the craft next year.
Lift-off atop an Atlas rocket from Cape Canaveral Air Force Station in Florida is scheduled for 06:36 local time (11:36 GMT) on Friday.
The automated mission to the ISS should last a week. The capsule will come home to New Mexico, using parachutes and airbags to make a soft landing on desert terrain in the early hours of 28 December.
Not since 2011, when the shuttles were retired, have Americans launched from their own soil; US astronauts have been hitching rides in Russian Soyuz capsules instead.
Starliner is the second of the new systems the American space agency (Nasa) hopes will restore independent human access to low-Earth orbit.
The other crew capsule in development is called Dragon, a product of California's SpaceX company.
Both should be approved for human use in the first half of 2020.
When that happens, Nasa will start purchasing seats in what will become commercial astronaut taxi services.
Contracting out space transportation in this way is designed to free up money for the agency to concentrate on the harder and more expensive task of getting people to the Moon and Mars.
"Nasa wants to be one customer of many customers in a very robust commercial marketplace for human spaceflight in the future," said the agency's administrator, Jim Bridenstine.
"The ultimate goal being we want to drive down costs, increase innovation, and increase access to space in a way that we've never seen before."
Starliner won't be completely empty on its ascent to orbit.
It will be carrying 270kg of supplies to the ISS - mostly food - and an anthropomorphic test device (ATD), or dummy, nicknamed "Rosie".
The ATD is covered in sensors to record the onboard environment. "She" will tell engineers how much discomfort a real astronaut might experience during the more violent phases of flight, such as on launch or during landing.
Starliner is going up on the well proven Atlas 5 rocket.
The latest version of this vehicle was developed originally only to launch satellites, but with 80 flights and no losses to its name - there is high confidence in its suitability to launch crew.
The Atlas family of rockets actually has quite a storied history in human spaceflight. They were used in the Mercury programme in the early 1960s.
"John Glenn was launched in the first (American) human orbital mission on an Atlas rocket in 62," remarked John Elbon, the chief operating officer for United Launch Alliance (ULA), which manufactures the Atlas.
Nasa has seeded Starliner and Dragon under its Commercial Crew Programme (CCP). Boeing and SpaceX were given milestone payments to encourage the development of their capsules.
The vehicles are somewhat late, however; they should have been flying in 2017.
That they are still at the demonstration stage is due in part to Congress squeezing the amount of money the agency could spend on the initiative. But there have also been technical set-backs, such as the explosive destruction of a Dragon capsule on a test stand.
"Building new spacecraft and developing hardware is really hard, right? Folks say it looks like it's taking a long time, but I think when you go back and look at development history over time, this programme's been doing a good job of meeting its obligations," said Nasa manager Kathy Leuders.
Assuming all goes well over the next week, Starliner should get the green light to ferry people to the ISS early next year.
The first crew has already been selected. It will comprise Mike Fincke and Nicole Mann, both Nasa employees, and the Boeing test pilot Chris Ferguson (Ferguson was the commander on the final shuttle mission and left Nasa to help Boeing develop Starliner).
Mr Finke, who is one of the most experienced astronauts in history with more than a year of his life spent in orbit, said the new astronaut taxis should open up a new era in human spaceflight.
"We crew, we're looking forward to commercial infrastructure in space because this means more flight assignments for us, which is what we as astronauts really live for. But it's also more flight assignments for the non-government astronaut types. This is a really interesting time," he told reporters on Thursday.