The origin of Sesto must be led back to the pre-Romanic period, as the numerous archeological founds discovered in the territory confirm.
The Roman spirit of Sesto is reaffirmed by its very same place-name: Sesto, in fact, was a statio, that is a post placed at the sixth milestone in the street which connected concordia with the Norico.
It knew a significant development during the Longobard domination, but then it was submitted by the incursions of a Germanic people called Ungheri. In the Middle Ages it lived a very bright period, with the annexion of the Abbey and of its territories to the feodal control of the Patriarchate of Aquileia, up to the Venetian military invasion of Friuli in 1418. With the Campoformido Treaty in 1797, the Venetian Republic came to an end and in the nineteenth century the territory of Sesto interlaced with the events of the Lombard-Venetian Reign up to the annexion to the Reign of Italy.
The present denomination of Sesto al Reghena dates back to 1867, when Friuli was annected to Italy, and it refers to the Reghena river, which flows through the village.