The first flight will take off from Melbourne for Los Angeles on Sunday, ending the plane's suspension on the ultra long-distance route due to safety concerns over its Rolls-Royce engines.
"As always, safety has been our first priority in assessing when and where to bring A380s back into service over the past month," Qantas chief executive Alan Joyce said.
"Only when we, our manufacturers and our regulators were completely satisfied that it was safe to begin flying the aircraft again did we resume A380 services, initially on London routes only," he said.
Qantas grounded its six A380s for intensive safety checks after a mid-air engine blast on November 4 sent shards of metal raining down on an Indonesian island and punched a hole in the wing of a Singapore-Australia flight.
It resumed limited flights to London in late November, but refused to relaunch trans-Pacific flights to Los Angeles until all concerns over its Rolls-Royce Trent 900 engines had been resolved. Trans-Pacific flights had been held off longer as the journey requires greater engine thrust.
Australian safety investigators said in December that an oil leak in a turbine may have caused the explosion, but were satisfied with the actions taken to prevent it happening again.
"The decision not to operate Los Angeles services allowed us to gain further operational experience before deploying the A380 on these routes," Joyce said.
"In close consultation with Rolls-Royce, we are now confident that we can begin flying the A380 to and from Los Angeles without any conditions on the use of maximum engine thrust" which is needed on the route, he said.
Qantas is still carrying out engine checks on its A380s as it gradually puts the world's largest passenger plane back into service. British engine-maker Rolls-Royce said in a statement it was "delighted" that Qantas had lifted its restrictions on the use of the A380s engines and returned them to normal service.
Qantas, which had flagged possible legal action against Rolls-Royce if no commercial settlement was reached over the incident, has replaced or modified at least 16 of its A380 engines following the explosion.