In 1594 Don Pedro married Catalina Enríquez de Ribera, daughter of the Duke of Alcala, one of the most prominent and wealthiest noble Houses of Andalusia, and a granddaughter, on her mother's side, of Hernán Cortés, the conqueror of Mexico. In 1594 Don Pedro inherited the dukedom. Although deeply indebted, in fact, under the Council of Castile administration, the estate of Osuna was only second by total wealth in Spain (after the Duke of Medina Sidonia). Before and after his marriage he was known for the reckless dissipation of his life. The scandals to which his excesses gave rise led to several orders of confinement or imprisonment. In 1602, apparently with the agreement of Don Juan Fernandez de Velasco, Constable of Castile, his uncle and political godfather, and one of the most powerful and outstanding personalities of the reign of Philip III, Osuna escaped from his confinement in the castle of Cuellar, accompanied by a servant, arriving in Brussels in October of that year.
Initially, he enlisted in the army of the Archduke Albert as a private, but soon he was given the command of two chivalry companies. In 1602 and 1603 he played a very important role in controlling and defusing the mutinies which erupted in Brabant among the armies of the Archduke, even financing the arrangements with the mutineers with his own money, raised in Flanders with the guarantee of his Spanish properties. Besides, he took a very gallant and courageous part in several important battles, being seriously wounded twice.
Another of Leti's legends says that in 1604 he went to London, as a member of the embassy sent by Philip III to James I to sign the Treaty of Peace, the ambassador being the Constable of Castile, but this is just another of the many Leti's inventions. In 1608, when the negotiations for the truce between Maurice of Nassau and Ambrosio Spinola had already begun in The Hague (he was against those negotiations, and took absolutely no part in them), he returned to Spain as a hero, being decorated with the Order of the Golden Fleece, the highest decoration given by the King of Spain as head of the Habsburg dynasty. In 1608 he arranged the marriage of his son, Juan, with the daughter of Cristobal Gómez de Sandoval, Duke of Uceda, the son and assistant of the Duke of Lerma, the Prime Minister and Valido of Philip III. The political meaning of such an agreement was indeed that he was accepted as a member of the Lerma's family and group of friends, the real ruling elite of the Spanish monarchy at the time.
On September 18, 1610 he was named viceroy of Sicily, and took possession of his post at Milazzo on March 9, 1611. During his Sicilian viceroyalty he organized a good squadron of galleys for the Royal Navy but also his own corsair fleet, in fact, the most important and best equipped corsair fleet sailing in the Mediterranean Sea at that time. He launched several successful expeditions against Berber pirates and harbours, as well as against the Turks. In 1616, the commander of the royal Sicilian fleet, Octavio de Aragon, achieved an important victory against Turkish galleys. Overall, Osuna set up a sizable naval force in Sicily and reinforced the military might of the island.
In 1616 he was promoted viceroy of Naples, and held the office until June 1620. The main problem for Spain in Italy was French and Savoyard ambitions on Milan, a key territory from the strategic point of view to maintain military communications between Spain and the Low Countries and other Habsburg territories in Europe. Between 1613 and 1618 Spain and Savoy were actually at war, Spain trying to contain the Duke of Savoy within the boundaries established after the Treaty of Cateau-Cambresis (1559), and the Duke, playing the role of Italian leader against foreign invaders (the Spaniards) trying by all means to enlarge his territories and, if possible, with French and Venetian help, to conquer Milan. The main provider of financial help to Savoy was Venice, and Osuna considered that to end the Venetian dominion of the Adriatic gulf and even to conquer Venice itself was convenient and feasible.
In May 1618 the Venetian authorities claimed to have uncovered a very serious conspiracy to sack the city and burn the arsenal, summarily executing a number of alleged participants (all of them French) but insinuating that the real and secret heads of the plot were Osuna and the Spanish ambassador to Venice, Bedmar. There can be no doubt about the hostility of Osuna against Venice, in fact Osuna had openly advised the King to attack Venice, and is very likely that he had a plan to that effect, but it is doubtful that the plan was ready for actual implementation when the Venetians took action. Anyway, the so called "Conspiracy of the Spaniards against Venice of 1618" has been a question open to discussion among historians for the last four centuries. Spanish and German historians have a tendency to deny that the conspiracy was real or was serious enough; French and Italian historians have the opposite view. The end of Osuna's government in Naples was very confused and tense. On the one hand, the nobility of Naples was increasingly hostile to Osuna, one of the main reasons being the economic burden imposed by the need to feed and lodge the big military force (12.000 soldiers) that Osuna had reunited in the town without the agreement of its representative bodies. On the other, because of Osuna's support to the political demands of the representatives of the low classes, "the people". In June 1620 the new temporary Viceroy, Cardinal Borja, former ambassador to Rome, took possession of the Viceroyalty against all formal rules, but Osuna accepted the authority of Borja and returned obediently to Madrid.
A few days after Philip III's death, in 1621, in what may be called a "purge" of the ministers of the new and very young king against Lerma's family and friends, Osuna was arrested by a decision of the State Council - the highest political and administrative body of the Spanish Monarchy - on a large and wide-ranging array of accusations (corruption, but also impiety, sexual misconduct, etc.) and remained under house arrest (imprisoned in castles or noble houses) until his death in September 1624. No sentence was ever pronounced, but the House of Osuna was out of the royal favour for three decades, and only during the reign of Charles II did it again play an important role in Spanish political life.
"Osuna el Grande," as he is called by Spaniards following a sonnet written by Quevedo as a personal tribute on the occasion of his death -- protagonist or inspirer of poems, comedies, dramas (among them the well known "Venice Preserved" by Thomas Ottway, 1682) and novels -- was one of the most original and audacious personalities of the Spanish imperial century. But considering his very sad end, his contemporaries wondered if he was perhaps more energetic than really wise.