Weathering of discharged mine tailings contaminates streams, rivers and floodplains with toxic metals on a vast scale. The magnitude of the problem depends on input tailings mineralogy, storage and dispersal, and climatic conditions. To better understand the mechanisms of long-term tailings weathering, a leaching column study was established, incorporating tailings and soil from Potosi, Bolivia, with the aim of modelling a 25 year field period. The Zn/Cd molar ratio of the tailings leachate water, initially 738 for the unaltered tailings, is highly variable over 15 model years of leaching, particularly in the mixed tailings-soil columns. Columns with soil have ratios as high as 2563, while pure tailings columns reach ratios of <376. We employ complementary techniques, involving atomistic computational modelling, leachate analysis and mineralogical characterization, to elucidate the mechanisms governing these incongruent Cd and Zn weathering dynamics.