The experimental Solar Impulse aircraft departed Washington early Saturday en route to New York on the final leg of its US tour aimed at showcasing the promise of clean energy, organisers said.
The plane, which runs on four electric propellers powered by an array of solar cells mounted on the plane's 63 meter wingspan, lifted off just before dawn from Washington Dulles International Airport at 0846 GMT.
At the controls was Swiss pilot Andre Borschberg, who has taken turns with compatriot Bertrand Piccard on different legs of the flight across the United States.
The Solar Impulse takeoff was broadcast live on the organizer's website, live.solarimpulse.com.
"Nine months of preparations and two months into the Across America mission - it almost seems untrue that it's all coming to an end," the organizers said on their website.
The single-person plane is expected to arrive at New York City's John F. Kennedy International Airport Sunday, July 7, around 2 am (0600 GMT).
Piccard, speaking to the team's in-house media group, said he hoped they could get permission to fly over New York while there is still light, and let residents of Manhattan and New Jersey get the "spectacular" view of the giant plane.
The aircraft is powered by 12,000 solar cells and flies under cover of darkness by reaching high altitudes during the day and gliding downward over long distances by night. It uses no fossil fuels.
Drawbacks include the tiny cockpit, vulnerability to turbulence and the lack of a toilet, so the pilots must relieve themselves by using an empty plastic water bottle on solo flights that routinely last 20-24 hours.
"I never find it too long," Piccard earlier told AFP. "When you are in the most revolutionary airplane, and you know that so many people are following your flight, so many people support your message about clean energy, it is just awesome to be in that plane."
The current model, the HB-SIA, is soon to be phased out as the Swiss team prepares to make test flights of the second-generation aircraft, the HB-SIB next year.
Piccard said the next plane will be 10 percent bigger, with more power, reliability, an auto-pilot function and a toilet so that pilots can make the four to six day long trips that will be part of its journey across the world in 2015.
The plane's American trip is just the latest in a series of groundbreaking flights across different parts of the world, including Europe and Africa.