A comprehensive investigation of the dynamical characteristics of proppant-laden flow systems in hydraulic fractures is important for the development of unconventional oil and gas resources. In this paper, we combine the micro-scale reconstruction technique and CFD-DEM method to numerically investigate the mobility and distribution rules of proppant-laden fluid in rough hydraulic fractures. To characterize realistic fracture surface morphology, six synthetic fracture models were assembled based on optical scanning data of real shale from three sets of hydraulic fracturing experiments. In order to accurately simulate the fluid-particle two-phase flow in rough fractures, the lift forces and particle rolling effect are considered in the CFD-DEM model. First, the effectiveness of the used CFD-DEM solver was validated by comparing it to the experimental data. We then examined mechanisms for the typical flow behaviors of proppant particles and fracturing fluid in smooth and rough fractures. Subsequently, the surface area ratio of the synthetic fracture model is adopted to characterize the cross-scale relationship between the micro-scale proppant distribution and fracture’s geometric features induced by the macroscale fracturing parameters (i.e., confining stress, fluid viscosity, flow rate, and sand ratio). Lastly, the parameter effects of the fracturing fluid, proppant particle, and fracture aperture on the dynamic characteristics of particulate flow in the hydraulic fracture are further discussed. In summary, the presented numerical model and findings can help better understand particle transport and distribution in real rock fractures and bridge the connectivity of the micro-scale particle flow and macroscopic fracturing parameter, which is vital for hydraulic fracturing process optimization.