Eighty Years' War: Siege of Antwerp: Antwerp is captured by Spanish forces under Alexander Farnese, Duke of Parma, who orders Protestants to leave the city and as a result over half of the 100,000 inhabitants flee to the northern provinces.

The Fall of Antwerp on 17 August 1585 took place during the Eighty Years' War, after a siege lasting over a year from July 1584 until August 1585. The city of Antwerp was the focal point of the Protestant-dominated Dutch Revolt, but was forced to surrender to the Spanish forces. Under the terms agreed, all Protestants were given four years to settle their affairs and leave the city. Many migrated north, especially to Amsterdam, which became the capital of the Dutch Republic. Apart from losing a high proportion of its mercantile population, Antwerp's trade suffered for two centuries as Dutch forts blockaded the River Scheldt up to 1795.

The Eighty Years' War (Dutch: Tachtigjarige Oorlog; Spanish: Guerra de los Ochenta Años) or Dutch War of Independence (1568–1648) was a revolt of the Seventeen Provinces of what are today the Netherlands, Belgium and Luxembourg against Philip II of Spain, the sovereign of the Habsburg Netherlands. After the initial stages, Philip II deployed his armies and regained control over most of the rebelling provinces. Under the leadership of the exiled William the Silent, the northern provinces continued their resistance. They eventually were able to oust the Habsburg armies, and in 1581 they established the Republic of the Seven United Netherlands. The war continued in other areas, although the heartland of the republic was no longer threatened. This included the origins of the Dutch colonial empire, which began with Dutch attacks on Portugal's overseas territories. At the time, this was conceived as carrying the war with the Spanish Empire overseas due to Portugal and Spain's being in a dynastic union.

The Dutch Republic was recognised by Spain and the major European powers in 1609 at the start of the Twelve Years' Truce. Hostilities broke out again around 1619, as part of the broader Thirty Years' War. An end was reached in 1648 with the Peace of Münster (a treaty part of the Peace of Westphalia), when the Dutch Republic was definitively recognised as an independent country no longer part of the Holy Roman Empire. The Peace of Münster is sometimes considered the beginning of the Dutch Golden Age. Nevertheless, despite achieving independence, from the end of the war in 1648 there was considerable opposition to the Treaty of Münster within the States General of the Netherlands since it allowed Spain to retain the Southern Provinces and permitted religious toleration for Catholics.