The analysis of lead (Pb) in lake-sediment cores is a useful method to reconstruct local histories of Pb pollution. Here, we use Pb concentration profiles from lake sediments to reconstruct local trajectories of pre-Colonial smelting from three metallurgical centres in the South American Andes: the Morococha mining district, Peru; the Bolivian Altiplano around Lake Titicaca; and the silver-mining centre of Potosí, Bolivia. The earliest evidence for Pb enrichment from smelting is on the Altiplano beginning ~AD 400, coincident with the rise of the pre-Incan Tiwanaku and Wari Empires. Coeval with the collapse of these Empires ~AD 1000, there is a dramatic decrease in Pb pollution on the Altiplano, suggesting metallurgical activity was closely tied to the Tiwanaku state. In contrast, metallurgy at Morococha, Peru and Potosí, Bolivia began ~AD 1000—1200, likely as the result of the diaspora generated by the collapses of Tiwanaku and Wari. The independent chronologies of these records suggest asynchronous metallurgical activity between mining centres, and local-scale control of mineral resources. Following Inca conquest of the Andes ~AD 1450, strong increases in Pb are noted at all three study sites, suggesting an increase in silver production to meet Inca imperial demand. Following Hispanic conquest (AD 1532), large increases in Pb pollution are noted at Morococha and Potosí, only to be superseded by industrial development. The records presented here have implications for the reconstruction of Andean prehistory, and demonstrate the sensitivity of lake sediment geochemistry to pre-Colonial smelting activity. The technique has much potential for exploring the timing and magnitude of pre-industrial metallurgy in the New World.