Dissolution of interfacial materials in spatially confined flow is an important physicochemical process. Here, we present a study of gold leaching, where the gold layer is removed from a microchannel wall within a high aspect ratio channel (8 μm × 4 mm cross-section; 1:500). The etchant is an aqueous solution of sodium thiosulfate, ammonium hydroxide, and copper sulfate. Optical transmission of the gold layer was used for quantitative, in situ, and real-time measurement of the layer thickness and its spatial uniformity along and across the channel. The onset of etching is not immediate, indicating that a passivation layer exists (even on ‘bare’ gold layers, where etching was delayed by approx. 2 min). Pre-treatment of the gold surface with an incomplete alkane thiol self-assembled monolayer (11-mercapto-1-undecanol) led to a later onset of etching and slower etching rate (5.5 nm/min) compared with that on ‘bare’ gold (6.2 nm/min). Flow profiles are reflected in the observed etch profiles. Upstream and downstream differences in etch rate are magnified for intermediate copper sulfate concentrations. This novel technique offers quantitative, in situ and real time monitoring of etching under controlled conditions in continuous laminar flow through microchannels, providing a valuable tool to understand various reactive processes in spatial confinement, such as heap or in-situ leaching in mineral processing.