He accompanied his mother to Brussels when she was appointed governor of the Netherlands, and in 1565 his marriage with the princess Maria of Portugal was celebrated in Brussels with great splendour. Alexander Farnese had been brought up in Spain with his cousin, the ill-fated Don Carlos, and Don John, both of whom were about the same age as himself, and after his marriage he took up his residence at once at the court of Madrid.
It was seven years, however, before he had again an opportunity for the display of his great military talents. In the meantime the provinces of the Netherlands had revolted against the arbitrary and oppressive Spanish rule, and Don John, who had been sent as governor general to restore order, had found himself helpless in face of the superior talent and personal influence of William the Silent, who had succeeded in uniting all the provinces in common resistance to the civil and religious tyranny of Philip. In the autumn of 1577 Farnese was sent to join Don John at the head of reinforcements, and it was mainly his prompt decision at a critical moment that won the Battle of Gemblours in 1578. Shortly afterwards Don John, whose health had broken down through disappointment and ill-health, died, and Farnese was appointed to take his place.
He was confronted with enormous difficulties, but he proved himself more than equal to the task. In military ability he was inferior to none of his contemporaries, as a skilful diplomatist he was the match even of his great antagonist William the Silent, and, like most of the leading statesmen of his day, was unscrupulous as to the means he employed so long as he achieved his ends. Perceiving that there were divisions and jealousies in the ranks of his opponents between Catholic and Protestant, Fleming and Walloon, he set to work by persuasion, address and bribery, to foment the growing discord, and bring back the Walloon provinces to the allegiance of the king. He was successful, and by the treaty of Arras, January 1579, he was able to secure the support of the 'Malcontents', as the Catholic nobles of the south were styled, to the royal cause. The reply to the treaty of Arras was the Union of Utrecht, concluded a few weeks later between the seven northern provinces, who abjured the sovereignty of King Philip and bound themselves to use all their resources to maintain their independence of Spanish rule.
Farnese, as soon as he had obtained a secure basis of operations in Hainaut and Artois, set himself in earnest to the task of reconquering Brabant and Flanders by force of arms. Town after town fell into his power. Tournai, Maastricht, Breda, Bruges and Ghent opened their gates, and finally he laid siege to the great seaport of Antwerp. The town was open to the sea, was strongly fortified, and was defended with resolute determination and courage by the citizens. They were led by the famous Marnix van St. Aldegonde, and had the assistance of an ingenious Italian engineer, by name Gianibelli. The siege began in 1584 and called forth all the resources of Farnese's military genius. He cut off all access to Antwerp from the sea by constructing a bridge of boats across the Scheldt from Calloo to Oordam, in spite of the desperate efforts of the besieged to prevent its completion. At last, on the August 151585, Antwerp was compelled by famine to capitulate. Favourable conditions were granted, but all Protestants were required to leave the town within two years. With the fall of Antwerp, for Mechelen and Brussels were already in the hands of Farnese, the whole of the southern Netherlands was brought once more to recognize the authority of Philip. But Holland and Zeeland, whose geographical position made them unassailable except by water, were by the courage and skill of their hardy seafaring population, with the help of English auxiliaries sent by Queen Elizabeth I, able to defy his further advance.
In 1586 Alexander Farnese became duke of Parma by the death of his father. He applied for leave to visit his paternal territory, but Philip would not permit him. He could not replace him in the Netherlands; but while retaining him in his command at the head of a formidable army, the king would not give his sanction to his great general's desire to use it for the reconquest of England. Farnese at first believed it possible to invade England successfully with a force of 30,000 troops, without significant naval protection, relying mainly on the hope of a native Catholic insurrection. Philip overruled him, and began the work that led to the Spanish Armada. As part of the general campaign preparations, Farnese moved against Ostend amd Sluis. Sluis was taken in August 1587. The Armada reached the area a year later, and after its defeat, Farnese broke up his camp at Dunkirk in September.
Farnese was to have turned his attention back to the northern Netherlands, where the Dutch had regrouped, but on December 231589, the French king Henry III was assassinated, and Farnese was ordered into France. He fought in France (1590 - 1592) in support of the Catholic opposition to Henry IV of France, and died at Arras in 1592.