The Dragon ship will be grabbed by the station robotic arm
California's SpaceX company will look to establish a piece of history on Saturday when it launches its Falcon 9 rocket from Florida.
The vehicle will lift the Dragon cargo
capsule into orbit on a mission to resupply the space station.
It will be the first time a commercial company has provided such a service.
Although billed as a demonstration, the mission has major significance because it marks a big change in the way the US wants to conduct its space operations.
Both SpaceX and another private firm, Orbital Sciences Corp, have been given billion-dollar contracts to keep the space station stocked with food and equipment. Orbital hopes to make its first visit to the manned outpost with its Antares/Cygnus system in the coming year.
Lift-off for the Falcon is timed for 04:55 EDT (08:55 GMT; 09:55 BST). It is going up from Cape Canaveral Air Force Station.
The ascent phase should last a little under 10 minutes, with the Dragon capsule being ejected just over 300km (185 miles) above the Earth.
The conical spaceship will then deploy its solar panels and check out its guidance and navigation systems before firing its thrusters to chase down the station.
A practice rendezvous is planned for Monday when Dragon will move to within 2.5km (1.5 miles) of the station.
If Nasa and SpaceX are satisfied that the vehicle is performing well, it will be commanded to fly up and over the outpost in preparation for close-in manoeuvres on Tuesday.
Unlike the Russian and European robotic freighters that drive all the way into docking ports on the International Space Station (ISS), Dragon will move itself to a position just 10m (32ft) under the platform where it will be grabbed by a robotic arm operated by astronauts inside the orbiting laboratory.
The arm will berth Dragon to the "Harmony" connecting module on the ISS. The crew are then expected to start unloading the ship's supplies of food and other consumables on Wednesday.
"There's no question that some people are putting too much weight on this flight because it is explicitly a test flight; and, indeed, we may not succeed in getting all the way to the space station," cautions Elon Musk, the CEO and chief designer at SpaceX.
"There are, hopefully, going to be two more flights to the space station later this year with almost identical configuration, so if this one doesn't succeed I'm confident one of the other two will. There should be no doubt about our resolve."
This mission is part of Nasa's Commercial Orbital Transportation Services (Cots) programme which was established to help shift some of the agency's traditional roles and activities into the private sector.
Nasa is provided seed funding of approximately $800m to SpaceX and Orbital to enable them to develop their rocket and capsule systems. Once they have reached the milestones laid out under Cots, the full ISS re-supply contracts will kick in.
For SpaceX, this is valued at $1.6bn (£1bn) and calls for a minimum of 12 Dragon missions to the ISS.
But the significance of the upcoming mission goes far beyond the delivery of astronaut dinners and replacement parts for the station.
Nasa is attempting to offload routine human spaceflight operations in low-Earth orbit to commercial industry in a way similar to how large organisations might contract out their IT or payroll.
The agency will now set performance targets; it will be up to the individual companies to work out how best to meet those targets.
At the centre of this philosophy is the use of "fixed-price" contracts, rather than the "cost-plus" model that has featured so prominently in space programmes of the past.
The intention is to free Nasa to concentrate more of its effort and funds on planning exploration missions far beyond Earth, to asteroids and Mars.
This means privateers picking up not just the unmanned cargo runs to the ISS, but the delivery and return of crew as well.
Vital statistics: How do the spacecraft compare?
To that end, SpaceX's capsule has been designed from the outset to carry people; and under another Nasa programme, the company is working to develop the onboard life-support and safety systems that would make manned Dragon flights feasible.
Lori Garver, Nasa's deputy administrator, observes: "We are at a brink of a milestone moment in our space history with the upcoming SpaceX launch - all part of this longer term strategy that will create high-quality jobs right here in America, reducing the cost of space transportation so that Nasa can spend our valuable tax dollars doing those very difficult things that the government is best at doing."
The "new era" is not without its detractors, however.
Elements in the US Congress would prefer to see the agency retain the intense oversight of the old approach.
These politicians say they have concerns about the safety of the new commercial systems, and question the value of seed-funding several companies in early-stage development work when only one or two completed systems are ever likely to win service contracts.
Last week, the House of Representatives passed a bill calling on Nasa to choose one company now, and put all its investment behind that particular outfit.
But making such a choice would be deeply flawed, believes Jeff Greason, the president of XCOR Aerospace and a leading proponent of commercial space.
"It is clearly possible 50 years after John Glenn for US industry to take people to orbit," he says.
"And given the fiscal realities, there is in my view simply no credible alternative to commercial crew transportation services, because trying to maintain a government-only ISS crew taxi will just break the budget.
"But competition is the key element in that strategy. Single-sourcing space transportation capability will just result in a new monopoly and will evolve the same cost structure as the old.
"Competition is the only tool we have to keep that from happening."
Since the shuttles were retired last year, America has no means currently of launching its own astronauts into space - seats must be bought for them on Russian Soyuz rockets.
SpaceX says Dragon could be ready to carry people within three years. Competing companies are promising similar timelines.
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