Mary married Archduke Maximilian in 1477, and the provinces were acquired by the House of Habsburg on her death in 1482, with the exception of the Duchy of Burgundy itself, which, with an appeal to Salic law, had been reabsorbed into France upon the death of Mary's father, Charles the Bold.

Maximilian and Mary's grandson, Charles V, Holy Roman Emperor and king of Spain, eventually united all 17 provinces under his rule, the last one being the Duchy of Guelders, in 1543.

On 15 October, 1506, in the palace of Mechelen, the future Charles V was recognized as Heer der Nederlanden ("Lord of the Netherlands").

After Charles V's abdication in 1555, his realms were divided between his son, Philip II of Spain, and his brother, Ferdinand I, Holy Roman Emperor.

Conflicts between Philip II and his Dutch subjects led to the Eighty Years' War, which started in 1568.

They were: The southern provinces, Flanders, Brabant, Namur, Hainaut, Luxembourg and the others, were restored to Spanish rule due to the military and political talent of the Duke of Parma, especially at the Siege of Antwerp (1584–1585).

The northern Seven United Provinces kept parts of Limburg, Brabant, and Flanders during the Eighty Years' War (see Generality Lands), which ended with the Treaty of Westphalia in 1648.

By the mid-16th century, the Margraviate of Antwerp (Duchy of Brabant) had become the economic, political, and cultural centre of the Netherlands after its capital had shifted from the nearby Lordship of Mechelen to the city of Brussels.

Bruges (County of Flanders) had already lost its prominent position as the economic powerhouse of northern Europe, while Holland was gradually gaining importance in the 15th and 16th centuries.

The fact that the term Netherlands has such different historical meanings can sometimes lead to difficulties in expressing oneself correctly.