Sediment fluxes at the estuary-sea interface strongly impact particle matter exchanges between marine and continental sources along the land-sea continuum. However, human activities drive pressures on estuary physical functioning, hence threatening estuarine habitats and their ecosystem services. There is an increasing societal need to better predict the potential trajectories of estuarine sediment fluxes resulting from natural and anthropogenic pressures, but the concomitance of human-induced and meteorological-induced changes makes the responses ambiguous. Therefore, this study explores a 22-year numerical hindcast, experiencing contrasted meteorological conditions and human-induced morphological changes (i.e., estuary deepening and narrowing), in order to disentangle the relative contributions of meteorological and anthropogenic changes on net sediment fluxes between a macrotidal estuary and its adjacent coastal sea. Our results highlight that intense wave events induce fine sediment (≤100 µm) export to the sea but coarser sediment (≥210 µm) import within the estuary. Remarkably, moderate to large river flows support mud import within the estuary. Over 25 years, the reduction of intense wave and river flow events reduces fine sediment export to the sea. In addition, the estuary morphological changes due to human activities increase fine sediment import within the estuary, shifting the estuary from an exporting to importing system. We propose a conceptualization of mud flux response to river flow and wave forcing, as well as anthropogenic pressures. It provides valuable insights into particle transfers along the land-sea continuum, contributing to a better understanding of estuarine ecosystem trajectories under global changes.