This article analyzes the rise of Portobelo as the most important center of the Spanish American slave trade from the 1660s to the 1730s. Portobelo's emergence was one of the most striking results of the structural transformation that the slave trade to Spanish America underwent between the 1640s and the 1650s. In these years, intra-American transimperial shipping displaced direct slave voyages from Africa to the Spanish Caribbean. By focusing on the elements that underpinned Portobelo's emergence, this essay shows how shifting transimperial connections affected the making and unmaking of the intraimperial circuits that supplied slaves to Spanish America. This approach reveals the inner workings, evolving links, and disputed hierarchies that interlocked port towns with inland cities and also structured the African diaspora in Spanish America and the emergence of a black Pacific.