This thesis uses the history of the extraction, trade and circulation of pearls in the Atlantic world as a guiding thread. It is interested in the work and political action of singular actors belonging to diverse indigenous, African and European populations involved in the exploitation of American pearls promoted in the southern Caribbean by the Hispanic Monarchy. In particular, it analyzes how, in the midst of global changes in the uses of material culture and its inseparable relationship with the history of labor and workers during the sixteenth and seventeenth centuries, the knowledge and political action of indigenous and African peoples contributed to shape the exploitation of this marine jewel. The thesis has been divided into two parts, with three chapters each. These parts have been named: (I) Politics and (II) Labor and workers. The first part uses the trajectories of indigenous women such as Isabel and Orocomay; Iberian officials such as Juan López de Archuleta; Africans and Afro-Portuguese such as Rodrigo and Domingo, to evidence the political action and the ways in which these actors and their peoples were instrumental in delineating the growing Atlantic geography of extraction, circulation, trade and labor flows that the pearling business connected. The second part focuses on the work and workers in the pearl fisheries, first in Cubagua Island and Río Hacha, then in Margarita Island and Cumana, analyzing the coexistence of different labor regimes and the changes in the forms of coercion, recruitment mechanisms and work systems, as well as the places of origin of these workers in the Caribbean, the Pacific and the West African Coast. This second part also considers the political and social transformations, as well as the connections and cultural exchanges between the Iberian Peninsula, the southern Caribbean and the West African coast. In this transcultural and global framework of connections, this work establishes a transversal dialogue with: (i) the global history of the Iberian empires, (ii) the global history of labor, (iii) the historiography of the pearl fisheries of the New World and, finally, (iv) the historiography of the indigenous and African populations. In this way, the experiences of Indians, Africans and Europeans in the pearl Atlantic are understood as an analytical window to understand the complexities and nuances of the forms of intercultural relations that characterized not only this region, but also the nascent modern world. This thesis proposes a new interpretation of the role of indigenous people and Africans during the sixteenth and seventeenth centuries in the pearl-connected Atlantic, showing how in the midst of complex scenarios marked by violence these actors with their own political agendas and their knowledge of navigation and the sea, as well as their struggles for freedom, limited, enhanced and transformed the development of pearl fisheries.