From the beginning of European overseas expansion in the fifteenth century, religious missions occupied an important place in the internal organisation of colonial empires. Their contribution to the ideological structuring of imperialism and the interaction with local populations is undeniable. With the emergence of the new imperialism and the scramble for Africa (after the 1870s), the missions, often anticipating the colonial political and administrative presence, enhanced their role as advocates of Europe’s “civilising mission”, above all through the education of the colonised peoples. For Portuguese decision-makers, the religious missions, with a multi-century tradition, had an important role in defending territorial claims overseas and promoting the empire’s nationalisation. However, the lack of national missionaries, Christianity’s inter-confessional competition in the nineteenth century and the emergence of international legal rules protecting missionary activities hindered Portugal’s strategies. Using sources from several archives (in Lisbon, the Vatican, and elsewhere) to emphasise the role of a transnational missionary staff and the international law of missions, this text intersects these aspects, examining their convergence in the controversial case of the exit and replacement of Jesuit missionaries in Mozambique in 1910–1911, to demonstrate the need to look at the missionary issues in the Portuguese overseas domains from perspectives that go beyond nation and empire.