It conforms, together with the cities of La Cruz , Yapeyú, and San Carlos, the Jesuit's Route, since they have their origins in the Jesuit Missions.

Santo Tomé's origin goes back to the XVII C. When it was founded by the Jesuit after the foundation of Yapeyú and La Cruz.

When the Jesuits were expelled in 1768, its decadence began and in 1817 it was razed by the internal fights, the natives and the Portuguese invasion.

The current city was founded in 1863. At the moment, it is a city with a suitable tourist infrastructure, it has modern hotels and a camping site located beside the Uruguay River; it offers all the necessary services. There are also several restaurants, discos and a casino.