In 1643, a Moluccan mestizo soldier named Alexo de Castro was arrested by the Holy Office of the Inquisition in the multicultural Manila barrio of Binondo. Suspected of secretly observing the Muslim faith in Manila, Castro faced inquisitorial investigations that culminated in his trial and punishment in Mexico. Based on evidence from Philippine, Mexican, and Spanish archives, this article examines Castro’s inquisition trial in the broader context of the seventeenth-century Hispano-Asian Pacific world that stretched from Mexico to Manila and the Moluccas. Within its permeable and shifting maritime boundaries, this transpacific cosmopolis was shaped by notions of Catholic universalism and orthodoxy present both in Spanish imperial ideology and in local adaptations. This article draws upon the Castro trial to reveal the tensions of this expanding world. On the one hand, Alexo’s mestizo genealogy and conversion to Catholicism, his work as a go-between in the Moluccas, and long career as a soldier for Spain and Portugal all reveal, on an intimate scale, the innumerable transits that interconnected this seventeenth-century world. On the other, Castro’s trial exposes the political-religious anxieties of Manila’s inquisitors, who saw in Castro a global threat posed by cosmopolitan New Christians – the moriscos, conversos, and indigenous converts whose adaptability and mobility helped to build this transpacific cosmopolis but also seemed to undermine it. By juxtaposing Alexo’s court arguments with those of his inquisitors, this study explores the limits of pluralism, cosmopolitanism, and exclusivism on this volatile seventeenth-century Pacific frontier.