Natural and human-induced toxic elements can accumulate in the environment, posing significant risks to human health and ecosystems. This study explores cave bat guano, an unconventional and relatively under-researched environmental repository, to reveal historical pollution trends and sources. Through trace elements analysis of a 1.5-meter-thick guano deposit from Zidită Cave (Romania), we track changes in mining and metallurgy from AD 1000 to 2012. We identified substantial pollution primarily from porphyry copper and Au–Ag–Te mines, but also impacts from usage of leaded gasoline and agricultural practices. Our record shows disruptions caused by the Bubonic plague around AD 1250 and a major surge ∼AD 1500. After the decline triggered by the European silver market collapse in AD 1525, our study reveals a brief mining revival. This resurgence was followed by a continuous decline lasting until the early 1800s, driven by socio-economic upheavals and recurrent outbreaks of the bubonic plagues. The Industrial Revolution sparked prolonged growth that lasted until AD 1989, only briefly interrupted by the Great Depression and World War II. Consequently, cave bat guano proves to be a critical resource for understanding spatial pollution patterns, both locally and regionally, and for identifying specific pollution sources.