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.
The current flight plan saw no threat from typhoons, a typical weather threat in Asia.
"I'm really confident we should be able to get through and find the right way," he said.
It is the seventh and longest section of the maiden solar-powered global circumnavigation, an attempt to promote green energy.
Nonetheless Solar Impulse 2 spent two months in China after arriving at Chongqing airport from Myanmar on March 31, where it had been due to make only a brief stop before continuing to Nanjing but was held up for weeks by weather issues.
After more than eight hours in the air, the plan was over the East China sea and Borschberg could be heard discussing light turbulence along the upcoming journey with the Solar Impulse team.
"For the Pacific, I need to be ready for the unknown," Borschberg tweeted before takeoff.
Each day on the Pacific voyage, Borschberg will experience altitudes of 28,000 feet, akin to the world's highest peak, and temperature changes of 55 degrees Celsius (almost 100 Fahrenheit) in the unpressurised, unheated Solar Impulse 2 cockpit.
At the same time he will only be able to catch the shortest of naps -- his seat doubles as a bed -- given the need to check the autopilot.
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