Solar Impulse 2's departure from China to Hawaii at 0240 am (1210 am IST) came more than a month after it landed in Nanjing on the night of April 21.
The plane delayed its originally planned departure from Nanjing on May 5 as its two pilots waited for the right weather conditions.
The journey from Nanjing to Hawaii is expected to take six days and six nights, with Andre Borschberg, 62, at the controls.
Bertrand Piccard, the plane's other pilot, said during his stay in Nanjing that the flight across the Pacific requires a period of clear weather and forecasts predicted typhoons on the ocean over the past couple weeks, state-run Xinhua news agency reported.
Powered by more than 17,000 solar cells installed on its wings, Solar Impulse 2 is circumnavigating the globe to promote green energy.
The solar plane has been featured in a number of events during its stay in China to promote new energy and materials.
After reaching Hawaii, the solar-powered airplane will fly across the US and stop in Africa before finally reaching Abu Dhabi, where it took off on March 9.
"I feel privileged to be able to try this flight...We have tools to adapt and we have the team to identify where to go. So I feel really confident to make it to Hawaii," Borschberg said.
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