William III was first and foremost a political animal, and in that sense the most internationally minded Prince of Orange ever. He left the governance of the Republic to his faithful followers, whom he had appointed to key posts. In 1700 the last Habsburg king of Spain, Charles II, died childless. Louis XIV of France thought he had a hereditary claim to certain Spanish possessions and managed without too much difficulty to place his grandson Philip, Duke of Anjou, on the Spanish throne. However, his claims were disputed by William III and by the Holy Roman Emperor, himself a Habsburg. The result was the War of the Spanish Succession, which broke out in 1702. In the same year, William himself died childless following a riding accident. In Britain, the throne passed to Anne, the sister of William's late wife, Mary Stuart. In most of the Republic, his death ushered in a second Stadholderless period. Friesland, however, retained its own Stadholder: Johan Willem Friso, whose grandmother was Frederick Henry's daughter. This aspect of his genealogy gave him a claim to become Stadholder of all the other provinces in the Republic. William III had in fact wanted to make him his successor, but the idea was opposed by the States of Holland.

The War of the Spanish Succession marked the start of a period of economic decline in the Republic. As in previous centuries, the southern Netherlands became the scene of incessant hostilities. Once again, the bone of contention was the territories subject to competing French, British and Dutch claims. And, once again, the people clamoured for a leader. In 1707 Johan Willem Friso, Stadholder of Friesland, was appointed to head the army. Many prominent figures in the Republic were in favour of appointing him Stadholder of the remaining provinces, but in 1711 he accidentally drowned while crossing the Hollands Diep. His son, Karel Hendrik Friso (later William IV), was born posthumously.

In 1713 the Peace of Utrecht was signed between Britain, Prussia, Portugal, Savoy and the Republic on the one hand and France on the other. Peace with Spain followed the year after. To obtain it, however, the Republic had to make major concessions. The southern Netherlands came under Austrian rule. The Republic retained only Venlo and Stevensweert and the right to garrison forts in the south. The principality of Orange reverted to France, but the title Prince of Orange was retained by William IV and his heirs.