In 1957–1959 he worked at La più grande storia mai raccontata ("The Greatest Story Ever Told"), a series of tales based on the Bible, and I dodici in cammino (a history of the Christian Church).
In 1969 he drew a western, Bob Jason, and started his most famous creation, Commissario Spada, a series featuring a commissioner of the criminal police of Milan, characterized by an unusual (for Italian comics) attention to realistic details, written by Gianluigi Gonano.
For the series De Luca introduced a number of graphical innovations, which he later used also for the comics version of three Shakespeare's masterworks, Hamlet, The Tempest and Romeo and Juliet, written by Raoul Traverso.
After the end of the Commissario Spada series in 1982, De Luca continued to work for Il Giornalino with the comics version of Il giornalino di Gian Burrasca, adapted by Claudio Nizzi, then to the Adventure on the Orinoco, written by Roberto Del Prà, and comics biographies of Totò and Marilyn Monroe.
These were followed by the science fiction series Paulus, with stories by Tommaso Mastandrea, depicting a historian living in a future dictatorship who, using a time machine, reproduces the life of St. Paul.