Diego de Deza was born in Toro, in the Kingdom of Castile, in 1444. He joined the Dominican order, studied theology and built a powerful career within the Spanish Church. A trusted figure at the royal court, he served as tutor to Prince Juan, son of Ferdinand of Aragon and Isabella of Castile. After holding several bishoprics, he became Archbishop of Seville.

Following Tomás de Torquemada's death, Deza was appointed Inquisitor General over much of Castile in 1498. His jurisdiction was extended across the Spanish kingdoms in 1499. Under his leadership, the Inquisition continued to pursue suspected heretics and converts accused of secretly practising their former religion. Deza supported the inquisitor Diego Rodríguez Lucero, whose severe methods prompted widespread unrest and allegations of abuse.

In 1506 Deza was compelled to delegate his authority, and Cardinal Cisneros succeeded him as Inquisitor General in 1507. Deza retained the archbishopric of Seville until his death in 1523. His career illustrates how religious justice, royal authority and personal influence were closely intertwined in the history of the Spanish Inquisition.