Potosí, the legendary silver mining city in colonial Upper Peru (modern Bolivia), emerged in the 16th century as a pivotal engine of early modern globalization. This paper argues that Potosí was not merely an economic hub but a crucial biological crucible where intense human exploitation, forced migration, and unprecedented environmental transformation forged a new biological blueprint for global interconnectedness. Through an interdisciplinary approach, drawing on historical demographics, bioarcheology, and environmental history, we examine the profound biological consequences of its silver production. The infamous mita system, alongside the introduction of African enslaved labor, precipitated catastrophic indigenous population decline through disease, overwork, and mercury poisoning. Simultaneously, it orchestrated an unprecedented exchange of pathogens, flora, and fauna, fundamentally altering the Andean ecosystem and the genetic landscape of its inhabitants. Potosí exemplifies how the rapacious demand for precious metals, fueled by emerging global markets, directly shaped human biological diversity, spread diseases across continents, and established enduring patterns of ecological modification, thereby acting as an early and brutal laboratory for a globally integrated biological system.