<p>Increasing anthropogenic pressures have significantly altered freshwater ecosystems worldwide, resulting in loss of biodiversity, reduced water extent, and shifts in aquatic vegetation dynamics. The Ganga Basin—one of the most populated basins—is experiencing rapid and abrupt urbanization over several decades, with significant loss of natural lakes and wetlands resulting in degradation of aquatic ecosystems. This study analyzed the long-term and multiple changes and the drivers of land use and land cover (LULC) of Karela Lake—an oxbow lake in the southern part of Lucknow, India, in the central part of the Ganga Basin, over the past 48&#xa0;years from 1976 to 2024 using a multi-layer perceptron neural network (MLP-NN) model. Karela Lake serves as a vital wetland ecosystem, supporting a variety of species and acting as a crucial water source for over a dozen nearby villages. The results indicate a 90.64% decrease in wetland area as the prominent land use change during 1976–2024. The lake is shrinking due to land encroachment and farming, with a substantial reduction in the lake margin. The Markov chain prediction method is used to predict the future LULC around Karela Lake. The year 2040 scenario shows that agricultural land and built-up area will increase substantially, with a decrease in scrub land and lakes’ wetted area. The major driving factors responsible for the degradation of the lake are the encroachment, land use change, pollution, intensive agriculture, and groundwater over-extraction. The study recommends a stricter land use policy, along with the demarcation of the lake’s boundary by the state wetland authority to prevent further encroachment and to support a diverse range of aquatic wildlife.</p>