After the conquest of the Byzantine empire by the Franks in 1204 A.D., Syros was under Venetian rule and, along with some other Cycladic islands, became part of the Duchy of Naxos of duke Marcos Sanoudos in 1207 A.D.

The small island of Syros, without particular opulence, seemed unimportant to its conquerors. Thus, it obtained a relative autonomy, which it kept until the duke's representative was replaced by a Byzantine governor. Syros contributed greatly to the survival of the Greek language, which continued to be used in religious services and for the official records.

The establishment of the village of Ano Syros, as we know it today, dates from that period. It was protected by the walls of its houses to the east, while to the west, a steep, rocky hillside formed a natural defence. It counted seven gates, called "portares", which were closed at sundown for protection against pirates.

At that time, a number of Venetians, common peasants, settled on the island and married local women. There is an opinion that the noblemen of Syros prefered marrying their daughters to foreigners, whom they considered to be more powerful and more respectable. In fact, there was no gentry to speak of as a result of migration and constant pirate invasions. This also made for a dramatic change in religion. Catholicism appeared on the island, but Greek language, customs and traditions remained, probably thanks to Greek mothers who raised their children in the Greek tradition, whereas foreign women became hellenised.

It is worth drawing attention to the difficult situation of the islands of the Aegean sea at that time. There was no protection from the Byzantines at a time when pirates constantly ravaged the island. Western powers could offer them no protection. Yet the western church was better organised, while the eastern church did not even have a bishop. Perhaps these are the reasons for the catholic presence on Syros to this day.

Obviously, there are other opinions, such as the theory of "enforced adoption of catholicism", or the opinion based on promises which the island's bishop Michail Psilos made to the Pope in order to preserve his position. Whatever the reason, we can conclude that, though catholicism is still present on Syros, its people are fundamentally Greek, keeping their language and following Greek-Byzantine religious ceremonies and customs. The characteristic observations of P. Zontanos from Hermoupolis, in 1842, ring very true, when he writes:
" The population of Syros is of the same heritage as that of the Greek people; in other words, they are Greeks and not Latins as they may think; they are Greeks as well as inhabitants of Ermoupolis. They share the same ethnos; they are Greeks , and not from other tribes or families; they are generations of the same motherland , of Greece."

In 1286 A.D., the duke of Tinos, Vartholomeos Gizi, invaded the island. Syros was saved thanks to the help of the king of Naples and his fleet, commanded by admiral Narsi di Togri.

In 1303 A.D., the island was given by the duke of Naxos, Francisco Krispi, as dowry to his daughter Petrounella, when she married duke Petro Zeno.

In 1408 A.D., the Florentine priest Christophoros Buondelmonti visited the island and described the situation he found there:
"People there use for food barley bread and goat meat. Because of the constant threat of pirates, their life is so desperate that the only reason that keeps them on the island is their children, their relations and their great attachment to their native place."

Stefanos Magnus wrote that, in 1484 A.D., its population counted only 400 people.

It is clear that Syros, along with the other Cycladic islands, suffered much, not only from pirate invasions, but also from conflicts between Frankish princes.