Upon the death of Frederick Henry of Orange (March, 1647), his only son succeeded to his titles and estates and also by virtue of the Act of Survivance to the offices of Stadholder in six provinces and to the Captain-Generalship and Admiral-Generalship of the Union. William was but twenty-one years of age and, having been excluded during Frederick Henry's lifetime from taking any active part in affairs of state, he had turned his energies into the pursuit of pleasure, and had been leading a gay and dissolute life. His accession to power was, however, speedily to prove that he was possessed of great abilities, a masterful will and a keen and eager ambition. He had strongly disapproved of the trend of the peace negotiations at Muenster, and would have preferred with the help of the French to have attempted to drive the Spaniards out of the southern Netherlands. The preliminaries were, however, already settled in the spring of 1647; and the determination of the province of Holland and especially of the town of Amsterdam to conclude an advantageous peace with Spain and to throw over France rendered the opposition of the young Stadholder unavailing. But William, though he had perforce to acquiesce in the treaty of Muenster, was nevertheless resolved at the earliest opportunity to undo it. Thus from the outset he found himself in a pronounced antagonism with the province of Holland, which could only issue in a struggle for supremacy similar to that with which his uncle Maurice was confronted in the years that followed the truce of 1609, and, to a less degree, his father after 1640.

Commerce was the predominant interest of the burgher-aristocracies who held undisputed sway in the towns of Holland; and they, under the powerful leadership of Amsterdam, were anxious that the peace they had secured should not be disturbed. They looked forward to lightening considerably the heavy load of taxation which burdened them, by reducing the number of troops and of ships of war maintained by the States. To this policy the young prince was resolutely opposed, and he had on his side the prestige of his name and a vast body of popular support even in Holland itself, among that great majority of the inhabitants, both of town and country, who were excluded from all share in government and administration and were generally Orangist in sympathy. He had also with him the officers of the army and navy and the preachers. His chief advisers were his cousin William Frederick, Stadholder of Friesland, and Cornelis van Aerssens (son of Francis) lord of Sommelsdijk. By the agency of Sommelsdijk he put himself in secret communication with Count d'Estrades, formerly French ambassador at the Hague, now Governor of Dunkirk, and through him with Mazarin, with the view of concluding an alliance with France for the conquest of the Spanish Netherlands, and for sending a joint expedition to England to overthrow the Parliamentary forces and establish the Stewarts on the throne. Mazarin was at this time, however, far too much occupied by his struggle with the Fronde to listen to the overtures of a young man who had as yet given no proof of being in a position to give effect to his ambitious proposals. Nevertheless the prince was in stern earnest. In April, 1648, his brother-in-law, James, Duke of York, had taken refuge at the Hague, and was followed in July by the Prince of Wales. William received them with open arms and, urged on by his wife, the Princess Royal, and by her aunt the exiled Queen of Bohemia, who with her family was still residing at the Hague, he became even more eager to assist in effecting a Stewart restoration than in renewing the war with Spain. The difficulties in his way were great. In 1648 public opinion in the States on the whole favoured the Parliamentary cause. But, when the Parliament sent over Dr Doreslaer and Walter Strickland as envoys to complain of royal ships being allowed to use Dutch harbours, the States-General, through the influence of the prince, refused them an audience. The Estates of Holland on this gave a signal mark of their independence and antagonism by receiving Doreslaer and forbidding the royal squadron to remain in any of the waters of the Province.

The news of the trial of King Charles for high-treason brought about a complete revulsion of feeling. The Prince of Wales himself in person begged the States-General to intervene on his father's behalf; and the proposal met with universal approval. It was at once agreed that Adrian Pauw, the now aged leader of the anti-Orange party in Holland, should go to London to intercede for the king's life. He was courteously received on January 26 o.s., and was granted an audience by the House of Commons, but the decision had already been taken and his efforts were unavailing. The execution of the king caused a wave of horror to sweep over the Netherlands, and an address of condolence was offered by the States-General to the Prince of Wales; but, to meet the wishes of the delegates of Holland, he was addressed not as King of Great Britain, but simply as King Charles II, and it was agreed that Joachimi, the resident ambassador in London, should not be recalled at present. The new English Government on their part sent over once more Dr Doreslaer with friendly proposals for drawing the two republics into closer union. Doreslaer, who had taken part in the trial of Charles I, was specially obnoxious to the royalist exiles, who had sought refuge in Holland. He landed on May 9. Three days later he was assassinated as he was dining at his hotel. The murderers, five or six in number, managed to make their escape and were never apprehended.