Developed and built by the state-owned aircraft giant Aviation Industry Corporation of China, the seaplane took off from the Zhanghe Reservoir in Jingmen, Hubei's province, at 8.51 a.m., and stayed airborne for about 15 minutes, the state media reported.
Xinhua news agency said the aircraft was piloted by four crew members.
Code-named "Kunlong", the AG600 made its maiden flight at the coastal city at Zhuhai in December 2017.
The AG600 is the third member of China's "large aircraft family" following the large freighter Y-20 and large passenger aircraft C919, Xinhua said.
Chinese President Xi Jinping sent a congratulatory note on the development, saying the successful take-off of the AG600 "marked another significant achievement through independent innovation by China's aviation industry".