Santa Fe de la Vera Cruz was founded by Captain Juan de Garay in the nearby site of Cayastá in 1573. The site is today a historical park containing the grave of Hernandarias, the first American-born governor in South America. The settlement was moved to the present site in 1653 due to the constant flooding of the Cayastá River. The city became the provincial capital in 1814, when the territory of the province of Santa Fe was separated from the province of Buenos Aires by the National Constituent Assembly, held in the city in 1853.
Santa Fe de la Vera Cruz is the commercial and transportation center for a rich agricultural area that produces grain, vegetable oils, and meats. The city is the site of the National Technological University – Santa Fe Regional Faculty,
Catholic University of Santa Fe (inaugurated in 1959), and the National University of the Littoral (first founded as the Provincial University in 1889, and which changed to its current name in 1919).
A suspension bridge was completed in 1924, though severe flooding partially destroyed it in 1983 (a second bridge, the Oroño, was opened in 1971). The cities location is still not immune to flooding, however. On April 29, 2003, the Salado, which empties into the Paraná near Santa Fe, rose almost 2 m (6.5 ft) in a few hours following heavy rainfall, and caused a catastrophic flood. No fewer than 100,000 people had to be evacuated, and large sections of the city remained under water more than a week later. That year, the suspension bridge was reopened, and in 2008, the city's historic grain silos were converted into the
Los Silos Hotel and Casino, and San Martín Street was converted to pedestrian use.
The city's historical role in the Argentine Constitution led national lawmakers to choose it as the site of Constitutional Conventions in 1949, 1957, and 1994.
Santa Fe rail station (1905), today the long distance bus station
Pedestrian San Martín Street