The successors of Obelerio inherited a united Venice. By the Pax Nicephori (803), the two emperors had recognised that Venice belonged to the Byzantine sphere of influence. Many centuries later, the Venetians claimed that the treaty had recognised Venetian de facto independence, but the truth of this claim is doubted by modern scholars. A Byzantine fleet sailed to Venice in 807 and deposed the Doge, replacing him with a Byzantine governor. Nevertheless, during the reign of the Participazio family, Venice grew into its modern form.

Though Heraclean by birth, Agnello, the first Participazio doge, was an early immigrant to Rialto and his dogeship was marked by the expansion of Venice towards the sea via the construction of bridges, canals, bulwarks, fortifications, and stone buildings. The modern Venice, at one with the sea, was being born. Agnello was succeeded by his son Giustiniano, who stole the remains of Saint Mark the Evangelist from Alexandria, took them to Venice, and made him the Republic's patron saint. During the reign of the successor of the Participazio, Pietro Tradonico, Venice began to establish its military might which would influence many a later crusade and dominate the Adriatic for centuries. Tradonico secured the sea by fighting Slavic and Saracen pirates. Tradonico's reign was long and successful (837–64), but he was succeeded by the Participazio and it appeared that a dynasty may have finally been established. Around 841, the Republic of Venice sent a fleet of 60 galleys (each carrying 200 men) to assist the Byzantines in driving the Arabs from Crotone, but it failed. In 1000, Pietro II Orseolo sent a fleet of 6 ships to defeat the Narentine and Croatian pirates from Dalmatia.

Republic of Venice in the Late Middle Ages

Venice became extremely wealthy through its control of trade between Europe and the Levant, and it began to expand into the Adriatic Sea and beyond. In 1084, Domenico Selvo personally led a fleet against the Normans, but he was defeated and lost nine great galleys, the largest and most heavily armed ships in the Venetian war fleet. Venice was involved in the Crusades almost from the very beginning. Two hundred Venetian ships assisted in capturing the coastal cities of Syria after the First Crusade. In 1110, Ordelafo Faliero personally commanded a Venetian fleet of 100 ships to assist Baldwin I of Jerusalem and Sigurd I of Norway in capturing the city of Sidon. In 1123 they were granted virtual autonomy in the Kingdom of Jerusalem through the Pactum Warmundi.. The Venetians also gained extensive trading privileges in the Byzantine Empire during the 12th century, and their ships often provided the Empire with a navy. In 1182, a vicious anti-Western riot broke out in Constantinople targeting Latins, and Venetians in particular.

Many in the Empire had become jealous of Venetian power and influence, and thus when the pretender Andronikos I Komnenos marched on the city, Venetian property was seized and the owners imprisoned or banished, an act which humiliated and angered the Republic. In 1183, the city of Zara successfully rebelled against Venetian rule. The city then put itself under the dual protection of the Papacy and King Emeric of Hungary. The Dalmatians separated from Hungary by a treaty in 1199, and they paid Hungary with a portion of Macedonia. In 1201, the city of Zadar recognized Emeric as overlord. 

The leaders of the Fourth Crusade (1202-04) contracted with Venice to provide a fleet for transportation to the Levant. When the crusaders were unable to pay for the ships, Doge Enrico Dandolo offered transport if the crusaders were to capture Zara, which had proven too well fortified for Venice to retake alone. Upon the capture of Zara, the crusade was again diverted, this time to Constantinople to avenge the 1182 massacre. The capture and sacking of Constantinople has been described as one of the most profitable and disgraceful sacks of a city in history. The Venetians claimed much of the plunder, including the famous four bronze horses that were brought back to adorn St. Mark's basilica. Furthermore, in the subsequent partition of the Byzantine lands, Venice gained a great deal of territory in the Aegean Sea, amounting to three-eighths of the Byzantine Empire. This included the islands of Crete ( Candia) and Euboea ( Negroponte); the present core city of Chania on Crete.

The Aegean islands came to form the Venetian Duchy of the Archipelago. The Byzantine Empire would be re-established in 1261 by Michael VIII Palaiologos but never again recovered its previous power and was eventually conquered by the Ottoman Turks. The Republic of Venice signed a trade treaty with the Mongol Empire in 1221. In 1295, Pietro Gradenigo sent a fleet of 68 ships to attack a Genoese fleet at Alexandretta, then another fleet of 100 ships were sent to attack the Genoese in 1299. From 1350 to 1381, Venice fought an intermittent war with the Genoese. Initially defeated, they devastated the Genoese fleet at the Battle of Chioggia in 1380 and retained their prominent position in eastern Mediterranean affairs at the expense of Genoa's declining empire.