Pilot Bertrand Piccard took off from the central city of Mandalay at 3.36 a.m. (22.00GMT SUNDAY) local time. He is heading for Chonqing in China, a journey that he says will take around 19 hours, according to the Irrawaddy news website.
The aircraft landed in Myanmar 10 days ago. It was due to depart earlier but was held up by bad weather conditions.
This leg will be one of the most challenging yet; temperatures in the unpressurized cockpit are expected to reach -20C as the plane soars above Chinese mountain ranges.
Piccard is taking turns to fly the one-man craft with his partner Andre Borschberg. They hope to set a world record by becoming the first people to circumnavigate the globe in a fuel-free plane.
The journey, which is due to be completed in 12 legs, started just under three weeks ago in Abu Dhabi.
The plane has already set two world records for manned solar-powered flight since then.
One was for the longest distance covered in a single journey, during the 1,468 km leg between Muscat in Oman and Ahmedabad in India.
The other was for highest ground speed; the plane reached 216km per hour on its way to Myanmar from Varanasi, India.
Solar Impulse 2 has a 72-metre wingspan, longer than a Boeing 747s. The wings are covered in 17,000 solar cells, which generate enough energy to propel the 2.3 tonne vehicle at average speeds of 70km per hour.
The team behind the Switzerland-based project plan to head to Nanjing, eastern China, shortly after landing in Chongqing. Once there they will begin the longest leg of the journey yet: a five-day flight across the Pacific Ocean to Hawaii.
The plane uses energy stored in a battery during daylight hours to power itself at night.