We conduct numerical simulations to investigate the role of aperture heterogeneity in early-stage karstification of a fractured carbonate rock. The fracture network is formed by a dominant set of persistent fractures and a secondary set of short fractures that abuts the dominant set. The variable aperture distribution priori to dissolution is derived from geomechanical simulation. We report that the extent to which aperture distribution affects karstification is jointly controlled by the far-field stress orientation, flow direction and structural hierarchy. When reactive flow occurs in the direction of the dominant fracture set, karst conduits only develop locally along a few large discontinuities preferentially oriented for frictional sliding, such that differential stress can produce shear dilatancy and enhance hydraulic transmissivity. In contrast, when reactive flow is along the direction of the secondary fracture set, the far-field stress loading has a negligible impact on the emergent dissolution pattern except somewhat impact on the onset time of breakthrough. In this case, the developed conduits exhibit much more tortuous pathways associated with numerous branches. Our results demonstrate that flow heterogeneity induced by geometrical complexities and geological conditions seems to play an essential role in the karst growth in fractured rocks. The research findings provide useful insights into the interplay among tectonic structures, in-situ stresses and karst cavities, which have important implications for underground engineering activities in karstified fractured rocks.