The Jesuit mission to enslaved Africans founded in 1605 in Cartagena de las Indias is amongst the most extraordinary religious developments of early colonial Latin America. By the time Alonso de Sandoval, S.J. and Pedro Claver, S.J. began their work to baptize and catechize the thousands of slaves who passed through Cartagena’s port each year, the Society of Jesus had already established a global missionary enterprise, including an extensive network of communication amongst its missionaries and colleges. Amidst this intramissionary context, Sandoval wrote De instauranda Aethiopum salute—a treatise informed largely by these annual letters, personal correspondences, and interactions with the diverse multitudes of people who could be encountered in this early colonial cosmopolitan city—aimed at promoting the necessity of African salvation. From East Asia to Latin America, Jesuits followed the example of their apostolic missionary, Francis Xavier, to bring the Catholic faith to non-Christian peoples. Through De instauranda and the Catholic Church’s collected testimony for the sainthood of Claver, we see how Sandoval and Claver, like other Jesuits of the time, arose as innovative and unique missionaries, adapting to their context while attempting to model the Jesuit missionary spirit. In doing so, this article posits, the historical-religious context of the early modern Atlantic world and global Jesuit missions influenced Sandoval and Claver to accompany enslaved Africans as a missionary theology.