The Portuguese Empire was the stage for one of the largest movements of enslaved people during early modern times. Almost two millions enslaved humans were violently carried from Africa in Portuguese vessels in the eighteenth century alone. Yet, in contrast to British or French slave traders based in Europe, for which a vast literature is available, little is known about the Lisbon traders. This paper aims at filling this gap by paying attention to the trajectory of two Lisbon slave traders: Domingos Dias da Silva and José António Pereira. In recounting their biographies and their business in Africa, Brazil, and Asia, we draw attention to the active role Lisbon-based slave traders played in the financing, organisation, and carrying of slave traffic, as well as the different institutional conditions they confronted when profiting from the commerce in humans. Domingos Dias da Silva became a key state contractor in spite of his poor origins, while Pereira featured as a global broker, connecting different markets in four continents. These two agents and their diverse characteristics help shed light on the slave trade, the context in which it expanded, and on the people who conducted this infamous commerce.