Pilot Andre Borschberg, 62, left the ground in Nanjing, in eastern China, heading for the US island of Hawaii, at about 2:40 am (1840 GMT), after extended delays awaiting a suitable weather window over safety concerns.
Lit by white lights on its wings, the plane rolled down the runway before climbing into a misty sky with its four whirling propellers nearly silent.
Ground crew members cheered as it took off.
"I cross my fingers and I hope to cross the Pacific," Borschberg told reporters just hours before the take-off.
"We have a good weather window, which means we have a stable corridor to reach Hawaii," he said, shortly before climbing into the cockpit to test the instruments.
"I'm really confident we should be able to get through and find the right way."
It is the seventh and longest section of the maiden solar-powered global circumnavigation, an attempt to promote green energy.
The journey began in Abu Dhabi in March and is scheduled for 12 legs, with a total flight time of around 25 days.
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