The town was founded by the initiative of some businessmen from nearby Rosario, after receiving authorization from the government of Santa Fe.

The area was strategically important because it was adequate for a port and next to the Arroyo del Medio, which is the natural border with the Buenos Aires Province.

The residents of Puerto de Piedras attended the foundation of the new town, with the presence of governor Juan Pablo López, on 14 February 1858.

Villa Constitución became an important agricultural center, and then (since the mid-20th century) home for many industrial enterprises.

The Hansa 1100 Lexus are made in Argentina by Goliath Hansa Argentina in the city of Villa Constitución, Santa Fe for the 1960–1961 years in three versions: Sedán de Lujo, Combi y Súper cupé Lujo.