The Tribunal of the Holy Office of the Inquisition began toward the end of the Reconquista and was intended to maintain Catholic orthodoxy in their kingdoms and to replace the Medieval Inquisition, which was under Papal control. It became the most substantive of the three different manifestations of the wider Catholic Inquisition along with the Roman Inquisition and Portuguese Inquisition. The "Spanish Inquisition" may be defined broadly as operating in Spain and in all Spanish colonies and territories, which included the Canary Islands, the Kingdom of Naples, and all Spanish possessions in North, Central, and South America. According to modern estimates, around 150,000 people were prosecuted for various offences during the three-century duration of the Spanish Inquisition, of whom between 3,000 and 5,000 were executed.

The Inquisition was originally intended primarily to identify heretics among those who converted from Judaism and Islam to Catholicism. The regulation of the faith of newly converted Catholics was intensified after the royal decrees issued in 1492 and 1502 ordering Jews and Muslims to convert to Catholicism or leave Castile, resulting in hundreds of thousands of forced conversions, the persecution of conversos and moriscos, and the mass expulsions of Jews and of Muslims from Spain. The Inquisition was abolished in 1834, during the reign of Isabella II, after a period of declining influence in the preceding century.