This paper reports on an ore-on-a-chip that enables efficient investigations of mineral leaching using real ore samples. Here, chalcopyrite (CuFeS2) ore samples are cut, polished flat, and sealed against a polydimethylsiloxane microchannel. The leach solution is collected for analysis, and the ore sample is then recovered for surface analysis. Compared to conventional bulk-scale leach tests, the ore-on-a-chip allows for faster, more efficient screening of leach parameters using real ore samples obtained from mine sites. Insight and optimization of leach conditions is demonstrated here for chalcopyrite, which has been extensively studied, yet leach performance is still strongly dependent on the origin of the ore. Two grades of chalcopyrite were chosen for this study (moderate and high purity), and the effect of ferric ion concentration and pH was studied in moderate and high purity chalcopyrite ores, respectively. The leach rate of Cu was faster in the presence of ore impurities (moderate grade) compared to the higher purity ore under the same conditions. The results also suggest that Fe is preferentially leached in the early stages to form an iron-deficient sulfide, according to X-ray photoelectron spectroscopy. Longer leach studies (48 h) reported no measurable surface passivation for the conditions studied. The ore-on-a-chip offers a new approach of case specific leach studies, which will enable rapid and tailored optimization of leach strategies for mineral processing.