Residual dense non-aqueous phase liquids (DNAPLs) trapped in fractured rock can sustain groundwater contamination through long-term dissolution. In rough fractures, aperture-field anisotropy controls preferential flow and residual source-zone architecture, causing interfaces of similar geometric area to differ in hydraulic accessibility. However, direct pore-scale evidence remains limited on how residual architecture and hydraulic accessibility jointly control dissolution pathways and interfacial-area-based mass-transfer scaling. Here, microfluidic experiments were used to quantify the co-evolution of residual DNAPL saturation, specific water–DNAPL interfacial area (as), and the image-derived apparent dissolution coefficient (Kapp). Aperture-field anisotropy and displacement history generated pool-dominated (PP), ganglia-dominated (GP), and mixed (MP) residual architectures with distinct dissolution pathways. Across Re = 0.395–6.583, flow rate altered dissolution kinetics and stage duration, but the dominant architecture-dependent response remained identifiable. PP systems underwent fragmentation-driven interface generation followed by contraction-dominated depletion, GP systems were dominated by ganglia contraction, and MP systems exhibited spatially sequential dissolution. GP trajectories generally occupied higher Kapp ranges, whereas MP trajectories occupied lower ranges. Aperture-field anisotropy modified residual morphology, pool elongation, interfacial-area evolution, and fragmentation persistence, indicating a pathway-level control on dissolution behavior. The proportional Kapp−as relationship did not hold universally: fragmentation-dominated stages produced scattered relationships, whereas contraction-dominated stages yielded more coherent but architecture-dependent responses. During GP Stage III, Kapp decreased more rapidly than total as, indicating reduced apparent transfer efficiency per unit geometric interface. These findings show that predictive models of DNAPL dissolution in fractured media should account for residual source-zone architecture, aperture-field anisotropy, dissolution stage, and the evolving hydraulic effectiveness of the water–DNAPL interface.