Afonso Mendes was appointed as the Latin Patriarch of Ethiopia by Pope Gregory XV in an effort to bolster the Catholic Church's presence in the historically rich and diverse religious landscape of Ethiopia. In May 1625, he arrived at Beilul, a critical point for his journey from Goa, India, following a long sea voyage and overland trek. Mendes's mission was not merely religious; it was deeply entwined with the political and social dynamics of the region, where various Christian sects existed alongside Islam and indigenous beliefs.

His work involved establishing stronger ties between the Ethiopian Christians, who were predominantly followers of the Orthodox faith, and the Roman Catholic Church. Mendes believed that by providing both spiritual leadership and practical support in governance, he could unify the Christian community in Ethiopia and counteract the rising influence of rival faiths. His arrival marked a pivotal moment, as he sought to advocate for Catholic doctrine while also addressing the local cultural context to ensure acceptance among the Ethiopian populace.

During his time, Mendes attempted to incorporate Western practices into the Ethiopian Christian traditions, which often met with resistance from Orthodox believers who were wary of foreign influence. Ultimately, he engaged in various diplomatic efforts with local rulers and religious leaders, navigating the complex landscape of Ethiopian politics, and leaving a lasting imprint on the region's Christian practices.