The airport was served during the 1960s from San Juan by Caribair, and then, rather heavily, by the Puerto Rican national air carrier, Prinair, during the 1970s and early 1980s.

American Eagle opened service from Luis Muñoz Marín International Airport in 1987, and Eastern Air Lines, not to be outdone by their rival American's feeder carrier, soon began services there too, with their own feeder airline, Eastern Metro Express.

Those plans never became a reality, but in 2003, the airport gained international status, when Fina Air picked up the route to Santo Domingo.

On November 8, 2004, American Eagle filed a 90-day notice of intent to the DOT to end service to Mayagüez on February 5, 2005 due to poor loads.

Eugenio María de Hostos Airport covers an area of 172 acres (70 ha) at an elevation of 28 feet (9 m) above mean sea level.