This study investigates the dynamics of land use and land cover (LULC) changes in the Densu Delta wetlands, a critical ecosystem in Ghana. Here, satellite images spanning from 1998 to 2023 were used to analyse the spatio-temporal patterns of LULC changes and their implications for water bodies, wetlands, vegetations, bare lands and urban areas in the Densu Delta wetland. Employing advanced techniques such as Markov chain modelling and artificial neural networks (ANNs), the research assesses and predicts LULC alterations. Significantly, the largest loss of LULC is observed in the Densu Delta wetland, where wetlands transition to waterbody cover type (14.02 km²). Model validation for 2023 attests to the accuracy of the model, boasting a correctness percentage of 70% and a kappa value of 0.74. In-depth analyses explore regional variations in the Densu Delta wetlands, revealing distinct patterns in the rates of LULC change before and after 2013. Notably, urbanization emerges as a prominent factor post-2013, with urban areas experiencing remarkable rates of change in the wetland. Transition matrices underscore the intricate interplay of different land cover classes over the years. Simulated LULC predictions for 2033 and 2043 highlight the urban land cover type as having the highest positive change, recording approximately 0.39% for the Densu Delta wetland. The wetland land cover in the Densu Delta wetland exhibit negative changes of about −0.52%. The synthesis of LULC data enhances our understanding of the complex interactions shaping these critical ecosystems. This research offers valuable insights for sustainable environmental conservation, emphasizing the pivotal role of informed urban planning policies. It also unveils potential challenges posed by climate change, advocating for a holistic approach to preserve these vital wetland ecosystems.