Despite Frederick Henry's victories, the southern Netherlands were still largely Catholic and in Spanish hands. Negotiations had already taken place with France about the division of the region. Frederick Henry died on 14 March 1647 after peace negotiations had opened in Münster between France, Spain and the Republic. The following year, these resulted in the Treaty of Münster, under which both the King of Spain and the Holy Roman Emperor recognised the United Provinces as a free and sovereign state. This brought an end to 80 years of warfare with Spain and terminated the formal ties between the Republic and the Holy Roman Empire. Since the existing front lines became the new national frontiers, the Republic gained sovereignty over a number of conquered territories, not only in Brabant, Flanders and Limburg but also in the East and West Indies. The territories in the southern Netherlands were placed under the direct authority of the States General and were thereafter known as the 'Generality Lands'.

Frederick Henry was succeeded as Stadholder by his son William II, who, in 1641, had married Mary Stuart, the ten-year-old daughter of the British King Charles I. Like his father, William II was fiercely opposed to peace with Spain. The States, however, were glad to be relieved of the financial burden of war and refused to go on funding the troops. William retaliated by marching on Amsterdam in an attempt to force them to keep the army up to strength. On 6 November 1650, however, he suddenly died of smallpox, just a week before the birth of his son, William III. Guardianship of the infant prince was initially shared between his mother, Mary Stuart, his grandmother, Amalia van Solms, and his uncle, the Elector of Prussia. However, after Mary Stuart died in 1661, the States of Holland assumed responsibility for the upbringing of the orphan boy, termed 'the child of state'. In 1653 Johan de Witt became Grand Pensionary of Holland and hence one of the most influential people in the Republic. The period of William III's minority, between 1650 and 1672, is known as the 'first Stadholderless period'.