This goes back to the Dutch Revolt and the Eighty Years' War - the Dutch 'war of independence' against Spain.

Background

Back in the 15th century the entire area that is now the Netherlands and Belgium (and Luxembourg and a bit of northern France) consisted of about 17 largely independent provinces (referred to as the 'Low Countries'), all of which had fallen under the control of Charles V, the Holy Roman Emperor and King of Spain. When Charles V abdicated, he left Spain and the 17 provinces to his son Philip II.

There was a lot of unrest in the Low Countries. Charles V had made efforts to centralise the government of the 17 provinces; Philip II continued with this. There was also religious strife, with Charles and Philip trying to prevent protestantism from spreading in the Low Countries.

Antwerp

At the time, Antwerp was probably the most important port in the Low Countries. The provinces of Flanders and Brabant were among the most prosperous of the Low Countries (along with Holland).

In the 1560s revolts broke out in the Low Countries. This is a complicated period, with towns and provinces choosing sides, switching sides, getting conquered, etc., at various times. Antwerp was on the rebel side for a bit, but got conquered by the Spanish forces sent to the Low Countries by Philip II to squash the revolt.

Around 1600, after a period in which the front lines were very fluid (if a front existed at all), the situation had stabilized with the rebels having control over the northern part of the Low Countries and the Spaniards over the southern part of the Low Countries. Antwerp was just barely in the Spanish sphere of influence, with the rebels controlling large parts of Brabant and small parts of Flanders.

The Scheldt

Antwerp's port had access to the North Sea via the Scheldt estuary. This never had been a problem, but with Antwerp being near the 'border' (it wasn't an official border yet) and the Scheldt flowing north, the actual estuary was under rebel control!

This was no coincidence. With Antwerp in Spanish hands, the rebels wanted to reduce its importance as a trading port. Any trade not going to Antwerp would go through rebel ports (Dordrecht, Amsterdam) instead. A lot of money could be earned this way.

The 'normal' situation was that the province of Flanders controlled the (south)west bank of the river and the province of Zeeland the (north)east bank. But when Antwerp had fallen back into Spanish hands, the rebels (who were in Zeeland) took control of the other bank, permanently occupied it, and blocked the Scheldt. This part of the Netherlands is still called "Zeeuws-Vlaanderen" ("Zeeland's Flanders")

The blockade

In the years after 1600 peace negotiations started between the rebels and the Spanish. These negotiations didn't lead to a peace, but they did lead to a truce, the Twelve Years' Truce. During this truce the Scheldt remained closed.

Near the end of the truce, the Spanish wanted to negotiate a permanent peace, but the Dutch declined. One reason (among others) was that a peace treaty would involve the opening of the Scheldt for trade. The provinces of Holland and Zeeland feared this would hurt their position as economic powerhouses in the area.

So the war resumed in 1621, for 27 more years. In 1648 a permanent peace was signed. By now the Dutch had an even more advantageous position and were able to force Spain to accept that the Scheldt would remain closed.

This situation lasted for one and a half centuries. It's only after the area got caught up in the aftermath of the French Revolution that the Scheldt was reopened.