The British group announced in March it was launching the new airline based out of Barcelona and connecting various US destinations, after Norwegian in September also said it would start cheap long-distance flights from the Spanish Mediterranean city.
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Level's first flight took off Thursday afternoon for a 13-hour flight to Los Angeles with a 314-seater Airbus 330.
IAG chose to base the airline out of Barcelona as the airport of this popular tourist attraction is also the home of its short- and medium-haul, low-cost airline Vueling, hoping this will attract passengers from one to the other.
The low-cost, long-haul model had not taken off until recently as it was not profitable.
But an increasing number of airlines are betting that the model will be a success on popular routes.
Norwegian, for instance, started long-haul flights from Paris to New York last summer.
Barcelona will be its fifth base for such flights as well as London, Bangkok and Amsterdam.
Icelandic airline WOW uses Reykjavik as stopover to offer low-cost flights between Europe and North America.