Solar Impulse is on its way from Varanasi in India to Mandalay in Myanmar (Burma).
The solar-powered plane is currently flying the fourth leg in its historic bid to fly around the world powered only by the Sun's rays.
Project chairman Bertrand Piccard has assumed the piloting duties, taking over from CEO Andre Borschberg, who flew leg three into Varanasi from Ahmedabad on Wednesday.
Thursday's trip is about 1,400km.
Piccard took off in darkness from Varanasi international airport at 05:22 local time (23:52 GMT). The route takes the plane out over the Bay of Bengal. The journey is expected to last about 20 hours.
The two pilots are taking it in turns to guide Solar Impulse on its circumnavigation of the globe.
So far, the pair have covered about 3,000km since beginning their adventure in Abu Dhabi on 9 March.
It will likely be another five months before they return to the United Arab Emirates, having crossed both the Pacific and Atlantic oceans in the process.
Thursday's leg has some tricky conditions to negotiate.
There are some difficult winds at high altitude. There is also a large mountain range that must be crossed about two hours before landing in Mandalay. The intention is for Solar Impulse to clear these peaks before sunset so that it can then get a clean descent towards the Myanmar city in the dark.
The Solar Impulse project has already set plenty of world records, including the greatest distance covered in a single solar-powered flight.
This was the 1,468km attained on leg two from Muscat in Oman to Ahmedabad.
The wingspan of the vehicle is 72m, which exceeds that of a 747 jumbo jet airliner. It does, however, only weigh 2.3 tonnes.
Its light weight will be critical to its success over the coming months.
So, too, will the performance of the 17,000 solar cells that line the top of the wings, and the energy-dense lithium-ion batteries it will use to sustain night-time flying.
The Pacific and Atlantic crossings will require Solar Impulse to fly non-stop for several days at a time.
This will put tremendous stress on Borschberg and Piccard, who will be permitted only short cat-naps on these long legs.
The Solar Impulse venture recalls other great circumnavigation feats in aviation - albeit fuelled ones.
In 1986, the Voyager aircraft became the first to fly around the world without stopping or refuelling.
Piloted by Dick Rutan and Jeana Yeager, the propeller-driven vehicle took nine days to complete its journey.
Then, in 2005, this time was beaten by the Virgin Atlantic GlobalFlyer, which was solo-piloted by Steve Fossett.
A jet-powered plane, GlobalFlyer completed its non-stop circumnavigation in just under three days.