Casilda began as an agricultural colony, created in 1870 by the Spanish merchant and banker Carlos Casado del Alisal, on land acquired from the ranch Los Desmochados.

On 11 November 1873 the colony officially became a town, named Villa Casilda after Casado del Alisal's mother.

In 1883 the railway Ferrocarril Oeste Santafesino reached the town, prompting an accelerated growth and bringing prosperity.

The economy of the area is based on agriculture, especially soybean, wheat and corn; cattle farming has been largely displaced to less fertile lands and feed lots by the advance of these crops.

Casilda also has flour mills, fertilizer factories, and many other industries, usually in the form of small and medium enterprises or cooperatives.