Why was Antwerp arguably the most important port in the world by the 16th century and not another port in a more powerful country?

Yo Lhexion, I’ll do my best to answer your question. I can’t really answer why other cities didn’t become as powerful and rich as Antwerp, but I can give you some pointers on why Antwerp itself grew to be one of the most powerful trading cities around. I’m gonna have to be a stereotypical historian and give your question a lot context and nuance before I actually answer it.

At around 1500, Antwerp was very much part of a powerful country, the most powerful country in Europe at the time: the Habsburg Empire! Since 1482, Antwerp and most of the Low Countries belonged to the Habsburg Spanish crown. Contrary to what some people seem to think, the Low Countries weren’t just some provincial backwater in the huge Habsburg empire. Spanish king and Holy Roman Emperor Charles V was born in the Flemish city of Ghent, some forty miles from Antwerp. He grew up in another Flemish city, Mechelen. In a certain sense, for the first 50 years of the 16th century, during the rule of Charles V, Antwerp itself and the Low Countries were more the centre of the Habsburg empire than its periphery. Charles V spent waaaaay more time in what is now Belgium then he did in Spain proper.

The fertile and densely populated lands along the Rhine, Meuse and Scheldt river were among the most economically prosperous in Europe. In the late Middle Ages, what is now Flanders was already a relatively rich and developed part of Europe, with many small and a few larger cities. Most of these cities thrived on trade with England and made cloth out of the wool they traded with the English. The Flemish cities would then paint or work this cloth and sell it on. Cloth was the big thing in Flanders in those days, and the industry attracted a lot of folks to Flanders, from all over Europe. Not just labourers, but also a lot of traders and bankers, ranging from Scots, to Portuguese, Germans to Italians and Norwegians to Russians.

Most of the wealth and immigration went to a few large Flemish cities: Bruges and Ghent being the most important. Just as Amsterdam and Antwerplater would, these cities rose to prominence as staple markets and banking centers. The 14th century is often seen as the ‘golden age’ of these cities. But then, as often happens when cities are growing rich, a new dude entered the scene. It was the duke of Burgundy – a powerful French noble. The Dukes of Burgundy slowly unified all the Low Countries under their rule. Before that, most of them had been independent duchies or counties. Now I won’t digress to much here, since the subject is Antwerp, but trading powerhouses Ghent and Bruges each revolted several times against the Duke. With each revolt ending in a loss for the Flemish cities, Ghent and Bruges slowly lost their economic prominence, as they lost special trading privileges with each failing revolt. Their decline was an important prerequisite for Antwerp’s rise.

Ok, what was it about Antwerp then? It was centrally located in the economically thriving Low Countries. It had very lenient trade regulations compared to other Flemish/Netherlandish cities. It had (indirect) economic ties with cities in the Low Countries, France and Germany through the system of Brabantian trades fairs – large fairs which were held multiple times per year, in Antwerp itself or in the close by city Bergen op Zoom. It had ties with cities on the Baltic shores, through it's good relation with the Hanseatic League. It was located on a natural and easily-protected harbour on the Scheldt river – which, in turn was close to the mouths of other large rivers, like the Meuse and the Rhine. While I wouldn’t say that one of these facts was ‘THE’ reason for Antwerp’s prominence, the combination of them all made Antwerp one of the boom towns of Early Modern Europe. Antwerp’s growth in wealth and power wouldn’t last for ever though – as religious troubles, a sacking by Spanish troops and the Dutch Republic’s blockade of the Scheldt river would soon reduce its stature as a trading centre. Nowadays, it is quite a lovely city, with its monumental buildings still donning the old town and it’s many high-quality beers being offered at very reasonable prices.