The Italian city of Venice was one of the largest cities in medieval and Renaissance era Europe. It was the center of the Republic of Venice, a maritime empire in the Mediterranean, and had one of Europe's largest ports for exotic goods (particularly from Asia), or luxury goods such as glassware. Impact of plague While its population was relatively small by modern standards, it is believed that Venice was among the five most populous cities in Western Europe in the given years between 1050 and 1650. The city's population did fluctuate over time due to devastating pandemics, and it is believed that Venice was one of the main points of entry for the Black Death in Europe. Venice was one of the hardest-hit cities during the Black Death; estimates fluctuate greatly across sources, but it is believed that the city lost around 40 percent of its population during the initial outbreak in the 1340s. Decline Furthermore, Venice lost roughly a third of its population during further plague pandemics (both introduced via war) in the 1570s and 1630s. Because of this, the population was kept fairly consistent across the given years between 1600 and 1800. The 18th century also saw the decline of the Venetian Empire, as other states gained power and influence in the Mediterranean. Venice also lost its importance as the entry point of exotic goods into Europe, as other European powers had already established their own maritime empires and trade routes across the globe. Eventually, the crumbling Venetian Empire fell to Napoleon in 1796, and its overseas territories were gradually taken by or split among various other powers. While the empire fell, the city itself continued to be a center for art and culture in Europe, and it has maintained this status until today. In 2021, Venice had a population of more than 250,000 people.

It is estimated that the largest cities in Western Europe in 1330 were Paris and Granada. At this time, Paris was the seat of power in northern France, while Granada had become the largest multicultural city in southern Spain, controlled by the Muslim, Nasrid Kingdom during Spain's Reconquista period. The next three largest cities were Venice, Genoa and Milan, all in northern Italy, renowned as important trading cities during the middle ages. In October 1347, the first wave of the Black Death had arrived in Sicily and then began spreading throughout Europe, decimating the population.

In 1500, the largest city was Paris, with an estimated 225 thousand inhabitants, almost double the population of the second-largest city, Naples. As in 1330, Venice and Milan remain the third and fourth largest cities in Western Europe, however Genoa's population almost halved from 1330 until 1500, as it was struck heavily by the bubonic plague in the mid-1300s. In lists prior to this, the largest cities were generally in Spain and Italy, however, as time progressed, the largest populations could be found more often in Italy and France. The year 1500 is around the beginning of what we now consider modern history, a time that saw the birth of many European empires and inter-continental globalization.