China Southern started the services on Tuesday (12 December) on 787-8 aircraft.
It is the only direct service between London and Zhengzhou, which has a population of more than 10 million.
The new service means Gatwick has 16 flights per week to China, with two daily services to Shanghai already operating.
China Southern joins Air China and China Eastern at Gatwick.
Stephanie Wear, vice-president aviation development at Gatwick, said: “China is a hugely important market for us, our passengers, and the regional economy, so it’s fantastic news for London and the South East to have China’s three major airlines operating from Gatwick for the first time.
“The new service to Zhengzhou will enable passengers to not only visit a fantastic city steeped in history and culture, but also visit family and friends, and connect to destinations across China and Asia.”