By the time of the colony, these lands were inhabited by the Mapené, Mocoretá, Guaiquiraró and Arubaí tribes.
The conquerors came from the north harnessing livestock and opening paths as long as the Jesuits came from Candelaria and they were organizing the missions. " La Posta de La Cruz " was the place pointed out by the settlers as the exchanging place of merchandises, mail, etc.
The people's settlement caused a serious disagreement between the town councils of Yapeyú and Corrientes due to the jurisdiction place.
The General Manuel Belgrano, during his trip to Paraguay arrived at the place and decided to award the post to Corrientes Government.
On November 16th 1810, the General Manuel Belgrano dictated the foundation ordinance with the name of "Nuestra Señora del Pilar de Curuzú Cuatiá".
The place where the Pago Largo Battle was fought is located to 10 Km from the city. The General Berón de Astrada died in the battle. It was declared historical place.
Near Curuzú Cuatiá there is a Fossils Deposit where many prehistorical fauna remains were found, and where the professor Francisco Podestad found out an skull of peculiar characteristics which was called "Ameghinnonterriun Curuzucuatinenze" that at the moment is in La Plata City Natural Historical Museum