After studying at the Liceo Artistico, Santo D'Amico moved on to study Architecture. While still studying, he presented his drawings and comics to several publishers. He had his first publications in Il Giornalino, doing lots of illustrations and "cinema novels" like 'Sifrid', 'Capitani Coraggiosi' and 'Guglielmo Tell'. While also cooperating with Paoline publishers, he began a collaboration with Il Vittorioso, for which he illustrated series like 'Na'Giamba', 'Speron d'Oro', 'Squadriglia Acrobatica' and 'Jolly', the latter in cooperation with Roberto Diso.
He also worked for the French market, cooperating mostly with Diso on so-called "petits formats". With Diso, he created 'Dan Panther' (1964-69), as well as 'Atoman contro Killer' (1965-66). He also worked on series like 'Perceval' (1959-60) and 'Lancelot' (also in cooperation with Diso, scripts by Jean Ollivier, 1965-87). D'Amico has illustrated 40 episodes of 'The Phantom'. He spent the final years of his career working for Il Giornalino.