[Objective] The Mekong Delta is one of the globally vital biodiversity hotspots, while long-term coastal geomorphic evolution driven by natural sediment transport and intensive anthropogenic interference has triggered prominent spatial differentiation in shoreline progradation and retrogradation across the delta. This study aims to quantitatively characterize the long-term spatio-temporal evolution characteristics of sandbars and shorelines in the Mekong Delta, identify the spatial heterogeneous patterns of coastal accretion and erosion, and further clarify the coupling driving mechanisms of natural hydrological processes and human activities behind delta geomorphic changes. The research is expected to provide reliable long-term baseline data and decision-making references for coastal ecological conservation, integrated water resource regulation, coastal risk prevention and regional sustainable governance in the transboundary Mekong coastal zone. [Methods] We acquired 35-year continuous Landsat remote sensing images covering the period from 1988 to 2023. The Normalized Difference Water Index (NDWI) was adopted to enhance the contrast between water bodies and terrestrial surfaces, and the Otsu’s method (maximum between-class variance algorithm) was applied to realize the automatic threshold segmentation of water-land boundaries, so as to extract multi-phase vector datasets of shorelines and sandbars accurately. On this basis, multiple quantitative indicators including sandbar total area and patch number, total shoreline length, inter-annual shoreline change rate and net shoreline movement distance were calculated to systematically reveal the temporal variation trends of sandbar geomorphology and the spatial differential features of shoreline dynamics between river channels and estuarine regions. Combined with historical sediment data, tidal-hydrodynamic records and regional socio-economic engineering statistics, We further summarized the dominant natural and anthropogenic driving factors responsible for the spatially differentiated geomorphic evolution of the Mekong Delta. [Results] During 1988-2023, the total terrestrial area of the Mekong Delta showed a significant increasing trend, accompanied by an obvious decline in the number of sandbar patches, which indicated the geomorphic evolution characteristic of small scattered sandbars gradually merging into large contiguous tidal flats. The total shoreline length exhibited dramatic inter-annual fluctuations within the 35-year research period, with a net total growth of 63.39 km across the whole study time span. Obvious disparities existed in shoreline change rates between both banks of inland river channels and estuarine zones. The net horizontal migration distance of shorelines presented spatially asymmetric progradation and discontinuous dynamic features, where most estuarine segments advanced seaward remarkably, whereas the coastal zone in the southeastern Ca Mau Peninsula suffered continuous shoreline retreat. The spatio-temporal evolution of the Mekong Delta shoreline displayed prominent spatial differentiation: estuarine coasts experienced persistent seaward accretion, while the southeastern coast of the Ca Mau Peninsula underwent severe erosion and retreat. Such two opposite geomorphic processes were jointly controlled by the long-term coupling effects of natural sedimentation, tidal hydrodynamic evolution, sea level rise, land subsidence, mangrove degradation, hydraulic engineering construction, tidal flat reclamation and groundwater over-exploitation. [Conclusions] This study systematically supplements a long-term sequential geomorphic monitoring dataset for the Mekong Delta and clarifies the spatially divergent evolution law of delta sandbars and shorelines under the joint disturbance of natural processes and human activities. The reduction in sandbar quantity alongside the growth in total delta area verifies that sediment convergence and small sandbar amalgamation dominate the geomorphic accretion process of the Mekong estuary, while asymmetric shoreline migration reveals that regional hydrodynamic redistribution and anthropogenic engineering have reshaped the traditional natural sediment transport pattern of the delta. From the practical perspective, the severe coastal erosion occurring in the Ca Mau Peninsula reminds local management authorities to strengthen mangrove wetland protection, restrict excessive groundwater exploitation and optimize the layout of coastal hydraulic projects to mitigate land subsidence and wave-induced coastal retreat. The research innovatively integrates sandbar morphological metrics and multi-temporal shoreline dynamic indicators to interpret delta geomorphic evolution, which can provide methodological references for long-term coastal geomorphic monitoring in other large river deltas worldwide.