The 502-seat superjumbo landed in rain at Sydney International Airport about 9.15am (AEDT) on Monday.
The superjumbo will replace the CZ326 A330 daily service, continuing to connect Sydney to the airline's hub, Guangzhou. The airline is the fourth to fly an A380 into Sydney.
The upgrade is expected to boost annual capacity on the Canton route by 40 per cent, or 162,000 seats.
At an official ceremony marking the inaugural flight, New South Wales Deputy Premier Andrew Stoner said it was a landmark day that would result in great economic benefits for Sydney and the state.
"This daily A380 air service, we expect will generate up to 5000 jobs here in NSW and contribute around $390 million to the Australian economy, each and every year," Stoner said.
"China now ranks as the largest international contributor of visitor nights and expenditure for NSW," he added.
"For the year ended June 2013, we saw an 18 per cent increase and around 400,000 visitors to beautiful NSW from China, and this contributed, we believe, some $1.3 billion to our state's economy."
Tourism Australia managing director Andrew McEvoy was also at the welcome breakfast at Rydges Airport Hotel.
He said the promotion of Australia to Chinese consumers, by both Tourism Australia and China Southern, was proving very successful.
"Australia now welcomes more than 700,000 Chinese visitors and it's growing at more than 20 per cent per annum," McEvoy said.
"China Southern is now carrying close to one in four Chinese visitors to our country."
The flight was the first A380 from a China-based airline to arrive into Australia.