This article concerns a significant yet underappreciated argument presented by Alexander Hamilton and Tench Coxe in their 1791 Report on the Subject of Manufactures in favour of protectionism: the argument from the diversity of natural talents. Whereas historians of economic thought have focused primarily on the Report’s articulation of the infant-industry argument, this study reveals that Hamilton and Coxe developed an equally powerful argument predicated on the diversity of natural talents, aptitudes, and dispositions that exist among individuals. According to this argument, since individuals possess distinctive talents, aptitudes, and dispositions, the cultivation of a diverse array of economic pursuits by using protective measures is necessary to allow individuals to exercise their unique qualities. By undertaking an examination of the primary texts of Hamilton and Coxe, including drafts of the Report, this article suggests that Tench Coxe, rather than Hamilton, was the architect behind the argument, having expressed similar ideas as early as 1789. The article then presents the case that this argument represents a significant departure from Adam Smith’s economic thinking. Whereas Smith downplays natural differences in individual talents and genius, Hamilton and Coxe see these differences as something fundamental and inherent to mankind, and this directly led to divergent conclusions concerning international trade policy. The article therefore challenges existing scholarship which has overstated Smith’s influence on American economic thought, and reveals how early American protectionist thought rested on distinctively different theoretical foundations that would influence later American protectionist thinkers in the nineteenth century.