The plane, which took off from New York's JFK airport around 2:30 a.m (1200 IST yesterday), is piloted by Swiss adventurer Bertrand Piccard, who is expected to spend approximately 90 hours - during which he will take only short naps - crossing the Atlantic.
"It's my first time taking off from JFK," Piccard said over a live feed from the aircraft as he headed off into the night sky en route to Spain's Seville Airport.
As of 9:30 p.m in New York (0700 IST today), the plane was near Canada's Nova Scotia and turning east to begin its ocean crossing after hugging the North American coast during the day.
Piccard noted in a blog post that he gets to experience a "Strawberry Moon" from the plane - an astrological phenomenon that occurs when there's a full moon on the Summer Solstice, the longest day of the year.
He will have "a bright full moon to guide me across the Atlantic Ocean in my solar-powered airplane."
The voyage marks the first solo transatlantic crossing in a solar-powered airplane and is expected to last four consecutive days and nights, depending on weather.
The plane, which is no heavier than a car but has the wingspan of a Boeing 747, is being flown on its 35,400- kilometre trip in stages with two pilots - Piccard and Swiss entrepreneur Andre Borschberg - taking turns at the controls.
The pair have flown alternating legs of the journey, with Borschberg piloting the flight's final Pacific stage, a 4,000- mile flight between Japan and Hawaii.
The 118-hour leg smashed the previous record for the longest uninterrupted journey in aviation history.
The plane, now on the 15th leg of its east-west trip, set out on March 9, 2015 in Abu Dhabi, and has flown across Asia and the Pacific to the United States with the sun as its only source of power.
"Smooth takeoff and all #Si2 systems have been checked here at the Mission Control Center for the #Atlantic Crossing," Borschberg posted on Twitter soon after Solar Impulse 2 was off the ground.
A few hours into the flight, which could be tracked via internet on the solarimpulse.com website, the flight team wrote that the flight was blessed with "a beautiful day without a single cloud".
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