Cardinal-Infante Afonso was a Portuguese infante (prince), son of King Manuel I of Portugal and his wife Maria of Aragon.

Manuel I, known as the Fortunate, was King of Portugal from 1495 to 1521. A member of the House of Aviz, Manuel was Duke of Beja and Viseu prior to succeeding his cousin, John II of Portugal, as monarch. Manuel ruled over a period of intensive expansion of the Portuguese Empire owing to the numerous Portuguese discoveries made during his reign. His sponsorship of Vasco da Gama led to the Portuguese discovery of the sea route to India in 1498, resulting in the creation of the Portuguese India Armadas, which guaranteed Portugal's monopoly on the spice trade. Manuel began the Portuguese colonization of the Americas and Portuguese India, and oversaw the establishment of a vast trade empire across Africa and Asia.