Originally constructed as Public School 72, this neo-Grec structure is one of the oldest intact school buildings in Manhattan, built to accommodate the growing immigrant population of East Harlem. Its architect, David I. Stagg, was Superintendent of Public School Buildings from 1872 to 1886. For about 20 years after the Board of Education closed the school in 1975, it provided classroom and office space for various institutions. In 1994-95, the building was converted to a cultural center.

The Julia de Burgos Latino Cultural Center is a designated New York City Individual Landmark.