Shales are low‐permeability caprocks that confine fluid, such as CO2, nuclear waste, and hydrogen, in storage formations. Stress‐induced fractures in shale caprocks provide pathways for fluid to leak and potentially contaminate fresh water aquifers. Fractured shales are also increasingly considered as resources for CO2 sequestration, enhanced geothermal, and unconventional energy recovery. Injecting reactive fluids into shales introduces chemical disequilibrium, causing an onset of a series of dissolution, precipitation, and fines mobilization mechanisms. The reactions have rapid kinetics and significant impact on porosity and permeability; consequently, flow and storage properties of caprocks. While previous research has explored the separate effects of these reactions, this study aims to uncover their simultaneous occurrence and collective influence. This study unveils these highly coupled transport and reactivity mechanisms by tracking and visualizing the reaction‐induced alterations in the matrix, microcracks, and fractures of shales over time. We conducted brine injection experiments sequentially at pH 4 and 2 in a naturally fractured Wolfcamp shale sample while simultaneously imaging the dynamic processes using X‐ray computed tomography (CT). CT images are validated by finer resolution images obtained using micro‐CT and scanning electron microscopy. We also tracked the sample permeability and fluid chemistry using brine permeability and inductively coupled plasma mass spectrometry, respectively. Findings show that fluid primarily flowed through fractures, dissolving reactive minerals and mobilizing fines on fracture surfaces. Dissolution of fracture asperities under confining stress resulted in the closing of fractures. Clogging in narrow fracture pathways, caused by fines accumulation, diverted fluid flow into matrix pores. Plain Language Summary Geological formations have significant potential to store CO2 and other fluids. Overlying low‐permeability shale caprocks prevent the upward movement of such fluids. Naturally occurring or induced fractures in caprocks may serve as potential leakage routes. Our research employs a range of experimental approaches to investigate the behavior of reactive fluids within shale rock fractures. Our findings indicate that, in the rock‐fluid system studied, fractures undergo a self‐sealing process due to a combination of geochemical and geomechanical phenomena. This discovery enhances our ability to assess risks and develop effective management strategies for fractured caprocks. Key Points Permeability responds to changes in fracture characteristics as a result of reaction and stress Fractures seal under confining stress when fracture‐propping minerals and fines dissolve or are displaced Fracture clogging diverts injected fluid into matrix pores where it is sequestered