The seepage-driven migration and clogging evolution of multi-sized particles within rock fractures profoundly affect the hydraulic stability and disaster mitigation in geotechnical engineering. To address the inadequate understanding of spatial differentiation and microscopic synergistic mechanisms of non-uniform particles within rough fractures, this study develops a three-dimensional seepage erosion model with realistic rough fractures based on the coupled computational fluid dynamics and discrete element method (CFD-DEM) to investigate the particle transport behaviors regulated by multiple parameters. The results indicate that particle size dictates the dynamic transport mode. Confined within low-velocity boundary layers, fine particles predominantly exhibit long-range continuous transport. In contrast, coarse particles undergo intermittent motion characterized by alternating local sliding and physical stagnation due to strong contact hindrance, which constitutes the intrinsic driver for the spatial differentiation of the system. Fracture geometry and hydrodynamic conditions exert strong nonlinear controls on the macroscopic mass loss behavior of the system. Increased roughness enhances the local geometric interlocking effect, leading to a step-like intermittent decay of the particle system; an enlarged aperture promotes a transition in the flow regime from a highly hindered local state to a sustained transport state. As the hydraulic gradient increases, the particle instability mode shifts from local slow loss at low gradients to global rapid flushing at high gradients. During the non-uniform erosion process, the mixed particle system exhibits pronounced spatial polarization and selective loss characteristics. Fine particles preferentially escape along dominant flow paths, while coarse particles are continuously hindered and displaced during migration, eventually evolving into a stable macroscopic retention zone in the mid-to-downstream region. Further microscopic analysis confirms that the formation of this retention zone is governed by three synergistic clogging mechanisms at the pore-throat scale: the circumferential wrapping of fine particles around coarse particle cores, the mechanical anchoring of fine particle clusters within narrow throats, and the synergistic arching induced by the boundary attachment of fine particles. These findings provide mesoscopic theoretical support for elucidating internal erosion mechanisms and seepage-induced catastrophic evolution within fractured rock masses.