San Zenone's territory was inhabited since prehistoric times, as attested by archaeological excavations.

In the Middle Ages it was part of the March of Treviso, and from the 10th century it was a possession of the bishops of Treviso. In the late 12th century it was acquired by Ezzelino II da Romano, and, in 1223, it was inherited by his son Ezzelino III. After the latter's death in 1259, his brother Alberico took refuge in the castle of San Zenone: here, after a long siege, he was captured by his enemies and killed together with his family the following year.