In the Southern Hemisphere, evidence for preindustrial atmospheric pollution is restricted to a few geological archives of low temporal resolution that record trace element deposition originating from past mining and metallurgical operations in South America. Therefore, the timing and the spatial impact of these activities on the past atmosphere remain poorly constrained. Here we present an annually resolved ice core record (A.D. 793–1989) from the high-altitude drilling site of Quelccaya (Peru) that archives preindustrial and industrial variations in trace elements. During the precolonial period (i.e., pre-A.D. 1532), the deposition of trace elements was mainly dominated by the fallout of aeolian dust and of ash from occasional volcanic eruptions, indicating that metallurgic production during the Inca Empire (A.D. 1438−1532) had a negligible impact on the South American atmosphere. In contrast, a widespread anthropogenic signal is evident after around A.D. 1540, which corresponds with the beginning of colonial mining and metallurgy in Peru and Bolivia, ∼240 y before the Industrial Revolution. This shift was due to a major technological transition for silver extraction in South America (A.D. 1572), from lead-based smelting to mercury amalgamation, which precipitated a massive increase in mining activities. However, deposition of toxic trace metals during the Colonial era was still several factors lower than 20th century pollution that was unprecedented over the entirety of human history.