First published in 1837, History of the Reign of Ferdinand and Isabella the Catholic is considered one of Prescott's most significant works and a classic in the field of historical literature. The book provides a detailed account of the reign of Ferdinand II of Aragon and Isabella I of Castile, who ruled Spain during the late 15th and early 16th centuries. Their marriage united the crowns of Aragon and Castile, leading to the consolidation of Spain as a unified kingdom. Prescott's work explores their political, military, and religious achievements, as well as their role in shaping the course of European history.

The book remains a valuable resource for understanding the history of Spain during a pivotal period. While some aspects of Prescott's interpretations have been critiqued or revised by modern historians, his work is still admired for its narrative quality and pioneering approach to historical scholarship.