Santa Fe city is located in the centre-east of Argentina. It belongs to the geographical region of plains called "pampa" in the Littoral zone.

This region exhibits a vast availability of natural resources which allows a strong integration into the economic and productive processes of the country. Furthermore, the Paraná River has an important influence on the area by generating the typical landscape of Argentine Littoral.

The city boundaries are constituted by two rivers (the Paraná River to the east, the Salado River to the west), the city of Recreo to the north, and the territory between the Santa Fe River and its confluence with the Salado River, a region plentiful of islands towards the Paraná River, in the south.
The territorial jurisdiction of the municipality extends over 26,800 hectares, 70% of which is an area occupied by rivers, lagoons, and marshes.