Solar Impulse 2 has taken flight across the Mediterranean Sea from southern Spain to Cairo, on the penultimate leg of its around-the-world journey.
The flight is expected to take 50 hours and 30 minutes.
Andre Borschberg will be at the controls for the final time on the journey that began more than a year ago, the Solar Impulse team said on Twitter.
Borschberg and fellow pilot Bertrand Piccard have taken turns flying the solar-powered plane on the circumnavigation experiment to draw attention to the potential uses of renewable energy sources.
The aircraft took off from Seville International Airport, the flight team said.
Solar Impulse 2 made history June 23 by becoming the first solar-powered aircraft to successfully cross the Atlantic Ocean. That flight from New York to Seville took 70 hours, nearly 20 hours less than originally estimated.
The carbon-fibre plane has a wingspan of 72 metres. The journey, which included many stops around the world, began in March 2015 in Abu Dhabi, the capital of the United Arab Emirates.
Piccard will pilot the return leg to there from Cairo.