Agricultural land-use changes pose challenges for land managers in terms of ensuring the implementation of local land-use plans. This paper aims to build a land-use change model named MEKOLUC (Mekong Delta land-use change) for simulating land-use changes under the impacts of socioeconomic factors (profitability of land-use types, societal impacts on neighborhoods) and environmental factors (soil, salinity, persistence of salinity). The salinity diffusion map was generated using GAMA software and employed Markov cellular automata to depict the spread of salinity under the influence of dike and sluice gate system operations. The land-use decision-making process was based on multi-criteria selection of the main factors, which were land suitability, land convertibility, density of land use in the neighborhood and profitability of land-use patterns. The input data for the case study were historical land-use maps from 2005, 2010 and 2015 of Soc Trang, a coastal province in the Mekong Delta. The model was calibrated using a land-use map from 2010 (with kappa = 0.86) and was verified with land-use maps from 2015 and 2020 with deviations from 0 to 19%. The simulated results showed that shrimp–rice farming areas have been shrinking, even though these are recommended as sustainable farming systems. Inversely, intensive rice crops tended to change to rice–vegetable crops, vegetable crops or perennial fruit trees, which are projected to be well adapted to climate and salinity intrusion by 2030. This case study shows that the developed model is an essential tool for helping land managers and farmers build land-use plans.