This inaugural test flight, operated by a Boeing 797-9 Dreamliner, departs New York on October 18 and is due to arrive in Sydney on Sunday morning.
On board will be 40-50 "guinea pig" passengers, pilots, crew, scientists and medical experts..
Most of the people on board the test flights will be Qantas employees, but there will be six Qantas Frequent Flyer volunteer passengers as well.
Qantas previously announced its goal of operating direct flights between London, New York, and three Australian cities -- Sydney, Brisbane and Melbourne -- by 2023.
Bjorn Fehrm, an aeronautical and economic analyst at Leeham News, tells CNN Travel there are several reasons travelers find the ultra-long-haul flight appealing, as opposed to a more typical two-part journey stopping in Dubai or Singapore.
There are no layovers, no extra journeys through customs and no transfer stress, he says.
"You can plan it so you fly overnight, and you could arrive to actually have a productive day the next day as well," says Fehrm. "It's going to be businesspeople that fly this way."
If the 19-hour flight becomes a reality, it's likely to cost travelers more.
"It's cheaper for the airline to do two separate flights," Fehrm says. "But some people are prepared to pay the extra price of that ticket."
The next test flight will take place in November, from London to Sydney, and there will be another New York to London flight happening before the end of the year.
After the test flights, the new planes will enter commercial service.
Researchers from Sydney University's Charles Perkins Centre, Monash University and the Alertness Safety and Productivity Cooperative Research Centre -- a scientific program backed by the Australian government -- will examine the impact of the long flight on those on board.
Singapore Airlines has redesigned its premium economy seats to prepare for its new 19-hour flight route between Singapore and New York.
Passengers in the main cabin will wear monitoring devices, and experts from the Charles Perkins Centre will study how their "health, wellbeing and body clock" are impacted by a set of variables that include lighting, food and drink, movement, sleep patterns and inflight entertainment.
Passengers have been advised to keep a daily log in the lead up to the flight and for two weeks after, to show how they feel and how they've coped with jet lag.
Pilots and cabin crew will also be monitored and keep sleep diaries. Cameras will be mounted in the cockpit to record pilot alertness.
Monash University scientists will focus on the flight crew, recording their melatonin levels before, during and after the flights, as well as studying brain wave data from electroencephalogram devices worn by the pilots.
"Ultra-long-haul flying presents a lot of common sense questions about the comfort and well-being of passengers and crew," says Alan Joyce, Qantas Group CEO, in the release.
"These flights are going to provide invaluable data to help answer them.
"For customers, the key will be minimizing jet lag and creating an environment where they are looking forward to a restful, enjoyable flight. For crew, it's about using scientific research to determine the best opportunities to promote alertness when they are on duty and maximize rest during their down time on these flights."
For some, the prospect of a 19-hour nonstop flight might sound unbearable.
"It was very much doubted in the previous generations of aircraft that this was something you'd want to do and that could be economically beneficial for airlines to do," Fehrm tells CNN.
If the flight comes to be, it's unlikely to significantly change the aviation industry, he says, pointing to the existing 17-hour flights between Singapore to New York operated by Singapore Airlines.
"In the world, we have 20,000 aircraft flying every day, and there are nine aircraft doing this kind of flight," he explains.
"It's an outlier for a very select group of people -- a prestige project," he says. "But it definitely makes sense in certain circumstances, and then it would be worth the cost."
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