The city of Santa Fe de la Vera Cruz, the capital of the eponymous province, is one of the oldest and most historically significant cities in Argentina. Its history began on 15 November 1573, when the Spanish conquistador Juan de Garay founded the settlement. Initially, the city was located elsewhere, in the area of modern-day Cayastá, but due to constant flooding and conflicts with indigenous tribes, it had to be relocated. This process began in 1651 and was completed approximately a decade later, when Santa Fe found its current, more secure location at the confluence of the Paraná and Salado rivers.
A key factor in the establishment of Santa Fe was its strategic geographical position. Its location on the navigable Paraná River transformed it into a vital river port and trade hub, connecting inland territories, including Asunción, with the Rio de la Plata region. Until the mid-19th century, the city also served as an important outpost, holding back raids by tribes from the Gran Chaco region. The city's political significance was cemented in 1853, when the congress that adopted the Constitution of the Argentine Republic gathered in Santa Fe, forever inscribing it into the country's history.
From the very beginning, Santa Fe's economy was closely tied to agriculture and trade. The city became a centre for a rich agrarian region specializing in the production of grain, meat, and dairy products. Early colonial architecture, examples of which still survive, reflects its status as an important administrative and cultural centre of the Spanish colony. Developed trade and political influence contributed to the formation of the city's unique character, which today combines historical heritage with dynamic development.