In 1259 Venice, together with much of Northern Italy, celebrated the defeat and death of the dreaded Ezzelino da Romano, tyrant of Padua from 1237 to 1254. Fighting nominally under the Imperial (Ghibelline) standard, Ezzelino had earned himself the reputation of an ogre (see Dante's Inferno), and Venice lent her support to the papal (Guelf) army that finally overthrew him. Yet Venice, child of Byzantium, had always turned her back on the unending wars of Guelf and Ghibelline in the rest of Italy, looking instead to the East. More significant, therefore, was the eviction of the Latin Empire of the East from Constantinople in 1261.

Founded 56 years earlier as a result of the infamous Fourth Crusade, the Latin Emperors had survived only with gifts from St Louis of France and loans from Venice, secured on Byzantium's most precious relic, the Crown of Thorns. St Louis later redeemed the relic from the Venetian bankers and built the Sainte Chapelle to house it. Venice soon reached an accommodation with the new Emperor Michael VIII Palaeologus, restoring most of her commmercial privileges and acknowledging her territories in the Levant.

In 1268, the Venetians took steps to ensure that their city would never be dominated by a single individual, as Padua had been by Ezzelino (and was shortly to be again, by the Carrara). They instituted the convoluted system of election to the dogeship which would endow the republic with the much-envied stability that lasted until the capture of the city by Napoleon in 1797.

Following the defeat of Ezzelino, Padua enjoyed a period of stability and prosperity which saw the construction of the Palazzo della Ragione and the Santo. By 1318, however, internal instability and threats from the Scaglieri dynasty in neighbouring Verona led the Commune to appoint Jacopo da Carrara as Capitano del Popolo.

In 1328 Padua fell to Cangrande della Scala. Cangrande's nephew, Mastino, continued the expansion of Scaglieri domains and in 1336 Venice, her trade with the mainland threatened, joined Florence in a league of states intent on his destruction. Marsilio da Carrara delivered Padua into the hands of the league, and by the peace treaty that followed the Carrara dynasty was restored to Padua; meanwhile Venice annexed a large and important area of the terra firma, including the March of Treviso.

In 1350 Francesco Carrara il Vecchio siezed power in Padua. From 1369 he pursued hostilities against Venice, and in 1379, in alliance with Genoa, captured Chioggia at the southern end of the lagoon itself. Chioggia was retaken by Venice in 1380, but in 1382 Francesco captured Treviso. Treviso was restored to Venice when Gian Galeazzo Visconti, ruler of Milan, took Padua in 1388; Francesco il Vecchio abdicated and was replaced by his son, Francesco il Novello.

Two years later, with Venetian help, Francesco il Novello re-entered Padua. Emboldened by the death of Visconti in 1402, Francesco challenged Venice once again, but was defeated. He was taken to Venice and executed; Padua was absorbed into the Venetian mainland territories.