American Airlines plans to launch non-stop flights between Miami and Barcelona from 3 April.
It will initially operate on the route five times a week, using Boeing 767-300 aircraft, and will increase this to a daily flight from 14 June.
"The addition of Barcelona further underscores the importance of our Miami hub and our commitment to its growth," said Peter Dolara, American's senior VP based in Miami.
American's trans-Atlantic joint venture partner Iberia will add a second flight between Miami and Madrid four times weekly from 25 March to complement the new service. American is a joint venture partner with Iberia and British Airways.
Iberia is currently the only carrier operating between Miami and Barcelona, schedules in Innovata show.