The Universidad Santo Tomás de Aquino was founded in 1538 in Santo Domingo, the capital of the colony of Hispaniola, present-day Dominican Republic. The creation of the university was authorized by the Spanish Crown, specifically King Charles I, as part of a broader effort to establish educational institutions in the New World. The founding of the university represented a major step in the Spanish colonial policy of fostering education and spreading Christianity among the indigenous populations and Spanish settlers.

The university was initially directed by the Catholic Church, reflecting the significant influence of religion on education during this period. The establishment of such an institution was intended to create a learned clergy and promote the teaching of Catholic doctrines. By providing a center for higher learning, it aimed to attract scholars and religious leaders to the region, which was critical for the Spanish Empire's control over its territories.

The curriculum at the Universidad Santo Tomás de Aquino included subjects like theology, philosophy, law, and the humanities, aligning with the European educational standards of the time. As the first university in the Americas, it played a pivotal role in shaping the educational landscape of the continent and set a precedent for other institutions that would follow.