The war that broke out in the Low Countries in 1568 marked the start of a period of eighty years of intermittent armed resistance against Spanish rule. In that year, an army of mercenaries under the command of William of Orange invaded the Low Countries in four places at once in an attempt to unleash a popular uprising. To fund the move, William had sold some of his Nassau estates. Mistakes on the ground led to the failure of the plan. Unable to take William himself prisoner, Alva seized his son Philip William, who was studying in Louvain, and sent him to Spain. William was never to see him again. William's associates, Egmond and Hoorne, were executed in Brussels on Alva's orders. In addition, Alva made himself even more hated by the nobility and the general populace by imposing a 10 per cent tax (known as the 'Tenth Penny') on all sales of movable goods. Not only was this a crippling measure for a trade-based economy like that of the Low Countries, it also meant that the provinces would lose control of the system of taxation. Consequently, it aroused such resistance that Alva was never in fact able to collect the tax. He had to accept the offer of a sum in compensation, which was raised by the provinces.

Following the failure of his attempted coup, William lived for some time in France, among the Huguenots (Calvinists). There he encountered Calvinism as a religion of the nobility and the burghers, whereas in the Low Countries it was practised chiefly by ordinary people. William himself was still a Catholic, and was to remain so for some time yet. He continued to advocate freedom of worship, despite the fact that his allies, the Calvinists, forbade Catholicism in the areas they had 'reformed'.

William made two more attempts at invasion, in 1570 and 1572. In the second of these he had the support of the French Huguenots on land and of the Sea Beggars off the coast. The plan was to launch a concerted attack in June. However, the Sea Beggars acted sooner than agreed and scored the first victory against the Spaniards by taking the small seaport of Brielle (Brill) in Zeeland on 1 April. Vlissingen (Flushing) and Veere fell soon after and the hoped-for popular uprising began in Holland and Zeeland. Representatives of the rebel towns met in Dordrecht and proclaimed William of Orange stadholder of Holland and Zeeland. He was not declared sovereign ruler, because he remained convinced that the revolt was directed not against the king but against the tyranny of his representative, Alva. This conviction is reflected in a line still sung as part of the Dutch national anthem, the Wilhelmus: "To the king of Spain I've granted lifelong loyalty". The Wilhelmus is actually a piece of religious and political propaganda written by an anonymous poet in praise of William of Orange and in defence of his leadership of the revolt.