ABSTRACT To what extent did Francis Drake’s circumnavigation of the globe influence empire formation in the late sixteenth century? In analyzing diplomatic letters of correspondence from the State Papers, this investigation reveals that Drake’s piratical activities, claims of English sovereignty, and the ensuing diplomatic controversy with the Spanish ambassador, Bernardino de Mendoza, forced the English Crown to use legal arguments rooted in the ius gentium (law of nations) and natural law to justify expansion into the Atlantic and Pacific oceans. During the dispute, both Mendoza and the English Crown variously invoked natural law and the law of nations to argue for justice and friendship. In testing these legal arguments, the Crown demonstrated that it had the capacity to counter Spanish claims for empire, which subsequently influenced imperial propagandists like Richard Hakluyt to promote English expansionism in natural law and ius gentium terms. In turn, the English Crown’s newfound confidence from the dispute manifested in its turn to reason of state and self-preservationist thinking in its international relations in the early 1580s, shortly before the outbreak of the Anglo-Spanish War (1585–1604). The dispute thus facilitated an ideology for empire rooted in natural law and the law of nations in the sixteenth century.