In situ recovery (ISR) has for several decades been considered an alternative mining method. It can substantially reduce the scarring of landscapes and eliminate tailings, dams, and waste rock while potentially minimizing energy consumption and carbon emissions. However, ISR applications beyond those for uranium have been limited. One key factor that limits the widespread application of the ISR approach is that many metals are largely hosted by orebodies with low hydraulic conductivity and/or a more pronounced hydrogeological and mineralogical heterogeneity. In those cases, the viability of ISR relies on a thorough understanding of the coupled transport and geochemical reaction processes and, more specifically, which subset of processes and parameters controls metal recovery. Laboratory experiments represent an essential first step toward developing this knowledge. Here, we describe a series of column experiments in which copper ore was leached during multistage experiments. Constrained by the collected data, we developed a reactive transport model and applied it to identify the main controls for copper recovery in the studied setup. The experiments showed copper recoveries above 60%, with a strong mineralogical control exerted by the composition of the copper mineral assemblage and a dependency of the copper recovery rates on the supplied lixiviant, i.e., the specific combination of acid and oxidant concentrations. The developed modeling framework was capable of accurately reproducing those observations and will provide a sound basis for optimizing copper recovery and establishing the reagent consumption.