Born in San Pietro Vernotico, Apulia, as a son of farmers; De Castro grew up on the family's 36-hectare farm.

He also chaired the Qualivita Foundation and currently runs the International Agricultural Policy Magazine edited by the Informatore Agrario in Verona.

From 21 October 1998 to 25 April 2000 he served as Minister of Agriculture and Forestry Policies in both governments chaired by Massimo D'Alema.

In this capacity, he led the parliament's negotiations in 2013 with the Council of the European Union on the Common Agricultural Policy (CAP) budget for 2014–2020.

In November 2000, President Carlo Azeglio Ciampi awarded De Castro the Cavaliere di Gran Croce al merito della Repubblica Italiana merit honour.