The Emirates aircraft, carrying 489 passengers in varying degrees of luxury, landed smoothly and on time after a 13-1/2-hour flight from Dubai.
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The plane, fitted out with lie-flat beds, flat screen televisions and spacious, windowed bathrooms in first and business class, is set to return to Dubai on Friday evening.
Emirates, owned by the government of Dubai, is the second airline to put the A380 into service, following Singapore Airlines, which started A380 flights to Sydney in October.
The plane, costing US$327 million (A$352 million) at list prices, did visit New York and Los Angeles in March last year for route-testing purposes, but Friday's flight was the first regularly scheduled arrival of an A380 in the United States.
With its huge capacity and relatively fuel-efficient engines, airlines hope the world's biggest passenger jet will be the most cost-effective way of serving high-volume routes linking big cities, especially in light of soaring oil prices.
Airbus, part of aerospace group EADS, says an A380 uses up to 20 percent less fuel per seat than a Boeing 747, and claims that when fully loaded and flying long distances it is more fuel efficient, per passenger, than a small family car.
The touchdown marks a hard-won victory for Airbus, which spent $10 billion and more than a decade on Europe's largest industrial project, in the face of widespread skepticism.