This article presents the first reconstruction of the relationship between conscience and empire in the Portuguese World between 1500 and 1650. It shows to what extent the foundation of the Mesa da Consciência (“Board of Conscience”), a royal council of theologians devoted to issues like war, commerce, conversion, and slavery, shaped the imperial ideology. In this context, “conscience” emerged as a keyword in the political vocabulary, reflecting the importance of moral theology for the political language in which the empire was conceived. It not only bolstered the hegemony of theologians but also encouraged the emergence of a missionary casuistry, which became increasingly independent of the central authorities in the kingdom and in Rome. Under the Habsburg domination (1580-1640) this system was dismantled and theologians lost their centrality at court. After the Restoration of 1640 some of the old institutions were recovered in name, but the old interconnection between politics and moral theology was not re-installed.