Don John advanced the causes of the Spanish Crown militarily and diplomatically in Naples, Sicily, Catalonia, the Netherlands, Portugal, Dunkirk, and other fronts.

[2][3] In 1642, the King recognized him officially as his son, creating him a prince (Serenity) and John began his life's career as a military representative of his father's interests.

Don John was sent in 1647 to Naples, then in the throes of the popular rising first led by Masaniello, with a naval squadron and a military force, to support the viceroy.

[4] He ordered his land and sea forces to blockade the rebel held city while Rodrigo Ponce de León, 4th Duke of Arcos inserted agents.

By the time Don John assumed command, most of Catalonia had been recovered and he had not much more to do than to preside over the final siege of Barcelona and the convention which terminated the revolt in October 1652.

When, however, he took a part in the leadership of the army at the Battle of the Dunes, fought against the French under Turenne and the British forces sent by Oliver Cromwell, he was decisively defeated and failed to raise the Siege of Dunkirk, in spite of the efforts of Louis, Grand Condé, whose invaluable advice he neglected, and the stubborn fight put up by his own troops.

[4] Even so, he might not have lost the confidence of his father, if Queen Mariana, mother of the sickly Prince of Asturias Charles, the only surviving legitimate son of the King, had not regarded him with distrust and dislike.