A comparison of model results with the chronostratigraphy of the Guadiana estuary’s post-glacial sedimentary infill enabled us to validate and complement a palaeoenvironmental reconstruction of estuarine evolution. Although it was approximate, the millennial/centennial timescale simulation also permitted us to establish a trustworthy base for decadal timescale forecasting. The simulation was performed by means of the Estuarine Sedimentation Model, which is an idealised, behaviour-oriented, GIS raster modelling tool. The model was subsequently run using sea-level/sediment accumulation rate data derived from interpreted borehole data. Morphological evolution during the 21st century was forecast using updated projections for sea level rise under the globalised economy and intensive use of fossil fuel (A1FI) scenario. The present maximum sediment deposition rate is approximately 0.65 mm/yr, and its decadal variability during the 21st century was assumed to be dependent mainly on the temporal variability of the marine sediment supply. The results obtained by hindcasting sediment infilling during the Holocene suggest that the proposed approach can be useful for simulating morphological evolution in sheltered environments in an estuarine system. According to the forecasts, the accelerated sea-level rise and the observed sediment supply deficit may result in submergence of salt marshes. The habitat loss would be more severe in the Spanish margin of the estuary than in the Portuguese margin. The simulated sediment deposition along the main channel shows the formation of longitudinal bars about 4 km in length. If the sediment supply into the estuary can be enhanced, the lower estuary may bifurcate.