San Isidro de Patulú origins date back to the pre-Hispanic period territory where its inhabitants were Indigenous groups of the Puruhá culture.

Back in the Spanish colonial era, it was known as Patulú Guayco, until it became an encomienda in 1560, with agriculture and livestock as its main economic activities.

Strong devotion to San Isidro Labrador, patron saint of farmers, shaped the religious and cultural identity of the community 

In the late 19th century, local leaders organized efforts to gain administrative autonomy from the parish of San Andrés. On January 27, 1894, San Isidro de Patulú was officially established as an independent parish.