The 16,200-kilometre test flight took 19 hours and 16 minutes, Qantas said on its Twitter account on Sunday.
Qantas QF 7879 departed New York's John F Kennedy Airport on Friday night and landed in Sydney's Kingsford Smith Airport on Sunday morning.
Forty-nine passengers, including Qantas executives, researchers, journalists, and crew members were on the flight, which was used to run a series of experiments to assess health and well-being onboard.
"This is a really significant first for aviation," Qantas CEO Alan Joyce said after arriving in Sydney.
Hubs and I hope to go to New York next June.