Accelerated oxidative weathering in a reaction cell (ASTM D 5744 standard protocol) was performed over a 33 week period on well characterized, sulfidic mine waste from the Kidd Creek Cu–Zn volcanogenic massive sulfide deposit, Canada. The cell leachate was monitored for physicochemical parameters, ion concentrations and stable isotope ratios of zinc. Filtered zinc concentrations (< 0.45 μm) in the leachate ranged between 4.5 mg L− 1 and 1.9 g L−1—potentially controlled by pH, mineral solubility kinetics and (de)sorption processes. The zinc stable isotope ratios varied mass-dependently within + 0.1 and + 0.52‰ relative to IRMM 3702, and were strongly dependent on the pH (rpH-d66Zn = 0.65, p < 0.005, n = 31). At a pH below 5, zinc mobilization was governed by sphalerite oxidation and hydroxide dissolution—pointing to the isotope signature of sphalerite (+ 0.1 to + 0.16‰). Desorption processes resulted in enrichment of 66Zn in the leachate reaching a maximum offset of + 0.32‰ compared to the proposed sphalerite isotope signature. Over a period characterized by pH = 6.1 ± 0.6, isotope ratios were significantly more enriched in 66Zn with an offset of ≈ 0.23‰ compared to sphalerite, suggesting that zinc release may have been derived from a second zinc source, such as carbonate minerals, which compose 8 wt.% of the tailings. This preliminary study confirms the benefit of applying zinc isotopes alongside standard monitoring parameters to track principal zinc sources and weathering processes in complex multi-phase matrices.