In general, the Ottoman threat to trade and the coasts of the entire Mediterranean, especially thanks to the alliance between the Sultan of Istanbul and the Barbary pirates, favored the rapprochement and collaboration between the two ancient rivals, e.g. in the Battle of Lepanto.

At the same time, the decline in the share of world trade passing through the Mediterranean during the Age of Discovery thwarted the Italian republics' ambitions for commercial dominance and the resulting tensions.

The traffic of these cities reached Africa and above all Asia, effectively inserting itself between the Byzantine and Islamic maritime powers, with which a complex relationship of competition and collaboration was established for the control of the Mediterranean routes.

The Crusades offered these cities, the so-called maritime republics (Amalfi, Genoa, Venice, Pisa, Ancona and Ragusa) the opportunity to expand trade, which was already active, with the Levant: thousands of inhabitants of these cities flocked to the East, creating warehouses, colonies and commercial establishments, supporting the Crusaders both logistically (e.g. the Genoese supplied the troops of Bohemond of Hauteville engaged in the Siege of Antioch) and with the supply of soldiers and military support.

At the beginning of the 13th century, the Mediterranean political-commercial balance was undermined by the Latin conquest of Constantinople (1204) during the Fourth Crusade which made Venice the undisputed master of trade with the East,[2] which by then had extended, in that period, to the Black Sea, a commercial hub along the Silk Road.

Constantinople was liberated from the Latins on the following 25 July and Genoa was able to establish itself there, then extending its influence into the Black Sea, where it reached Pontus (northern Anatolia) and the Crimea, while Venice was formally expelled (although the Venetian quarter of the metropolis continued to be used and populated).

This first open clash between Venice and Genoa, which originated well before the Byzantine reconquest of Constantinople and due to the inevitable collision between the two thalassocracies, came to be known as the War of Saint Sabas and was the prelude to a conflict that dragged on with alternating events until the threshold of the 15th century.

The management of these territories was "mixed": in Constantinople, power was centralized in the hands of a podestà who was responsible, theoretically, for everything that happened in Romania; in the Aegean, as anticipated, Venice preferred to enfeoff its nobles and citizens by creating a network of vassalage on the model of what was done by the French Christian potentates with whom it had collaborated in the Fourth Crusade.

In 1284 Genoa took possession of Corsica and part of Sardinia following the victory against Pisa in the Battle of Meloria (in which the Pisan fleet was commanded by a Venetian, former consul of Constantinople Alberto Morosini[3]).

It originated from a dispute between merchants in Acre (then the capital of the Kingdom of Jerusalem since the Holy City had been reconquered for the Muslims by Saladin), a key business center for all trade and interests, especially Italian, in Levantine coast.

[4] In 1261, with the signing of the Treaty of Nymphaeum between Genoa and the Nicaean emperor Michael VIII Palaiologos, the reconquest of Constantinople from the Latins supported by Venice took place, as anticipated.

The war ended in 1270 with the Peace of Cremona, mediated by Louis IX of France and Pope Clement IV who wished to organize the Eighth Crusade and needed the Venetian and Genoese fleets for this undertaking.

[7] Following the peace, Venice increased its power in what remained of the Kingdom of Jerusalem but was unable to prevent the relaunch of Genoese trade in the Byzantine world and the establishment of their commercial dominion in the Black Sea which would last until the Ottoman conquest of Constantinople (1453).

Despite the Byzantine-Venetian truce of 1285, the Byzantine emperor Andronikos II Palaiologos immediately sided with the Genoese, arresting the Venetian survivors of the massacre, including bailo Marco Bembo.

[3] In 1298, the Genoese fleet under the command of Lamba Doria entered the Adriatic and engaged the Venetians in the bloody Battle of Curzola, the largest and most challenging maritime clash between the two republics to date.

At the beginning of the 14th century, relations between Genoa and Venice were still in a state of tension (in 1304 the Genoese occupied Chios with the approval of Byzantium) but the political upheavals in Crimea managed to make the two thalassocracies unlikely allies.

Dissatisfied with this trade fueled by steppe kidnappings to provide an army to his enemy the Mamluks, Khan Toqta of the Golden Horde arrested the Genoese residents of Sarai Berke and besieged Caffa.

After two years of siege, the Mongols were forced to retreat after being decimated by the plague, which also infected the Genoese after Jani Beg decided to throw plague-ridden corpses over the city walls.

A combined Venetian-Catalan fleet under Niccolo Pisani and the Catalan Ponce de Santapau arrived soon afterwards and joined forces with the Byzantines, and the bloody battle of the Straits was fought in the Bosphorus in February 1352.

This induced the Genoese to help John's son Andronikos IV to seize the throne, in return for the transfer of the island to Genoa, initiating a new war between the two republics.

Its chronic political instability became acute after 1390, contributing to the acceptance of French sovereignty in 1396, the first of a series of prolonged bouts of foreign rule during the fifteenth century, which reduced its freedom of action.

After 1400, the expansion of Aragonese power in the western Mediterranean posed an increasing threat to Genoa, which led to a series of full-scale wars (1420–26, 1435–44, 1454–58) and remained a major preoccupation until the death of Alfonso V of Aragon in 1458, taking priority over the old rivalry with Venice.