The area was inhabited since the prehistoric age: the archeological researches that have taken place during the 20th century have revealed traces of a Neolithic village in the neighbourhood of Chiesanuova, on the left bank of the river Piave Moreover, significant traces of centuriation and the presence of an articulate road network make suppose that the zone was inhabited also during the Roman age.

During the Modern era, the Republic of Venice started some reclamation interventions in the area of Basso Piave and assigned the management of the territory to a functionary.

The public authority was held by a functionary nominated by the Doge, the Ducal Vicarial, who had the duty to pledge the oath of allegiance to the Republic and to reside in San Donà.

With the annexation of Venice and its dependency to the Napoleonic Italian Kingdom, on 1 May 1806 the Department of Adriatic was created and the town of San Donà was part of it as administrative center of the territory of the same name.

At the beginning of the 19th century, were created the first consortiums for the reclamation of the swampland at east and south of the urban center, while the city was significantly increasing its administrative functions.

The city of San Donà was part of the Lombard-Venetian Kingdom from 1815 and during the Austrian domination it kept its position of county seat of the district.

On 25 April 1945, in the presence of six thousands German soldiers, was proclaimed the insurrection of the city, and in the same day, the town of San Donà was free.

San Donà is now a crucial point of the transport infrastructures between Vento and Friuli Venezia-Giulia, crossroad between the industrial development zone in the area of Treviso and the tourist attractions of Cavallino-Treporti, Jesolo, Eraclea and Caorle.

Seven centuries ago, during the Middle Ages, San Donà and the close village of Musile di Piave were two small communities of the wetland situated north-east of Venetian Lagoon.

Hence the compromise: San Donà kept the name of the saint, but its population must reward that one of Musile with two capons ("gallos eviratos duos") on 7 August each year.