Under the context of a major inter-basin water transfer project, the evolution patterns and driving mechanisms of land use in water source areas were investigated. The middle-route water source area of the South-to-North Water Diversion Project was selected as the study region. Based on the 30-m annual land cover products of China from 1999 to 2019, GIS spatial analysis, land use transfer matrices, and land use change feature indices are employed to systematically characterize the spatiotemporal dynamics of land use/land cover change over the past two decades. A Logistic regression model with spatial lag terms was constructed to quantitatively identify the dominant drivers of different land type conversions from natural, climatic, locational, and socioeconomic dimensions. The results show that significant structural adjustments are observed in land use patterns, with continuous expansion of forest, water, and impervious surfaces, and notable reduction of cropland, shrubland, and grassland, overall exhibiting phased evolution driven by ecological restoration, urbanization, and engineering activities; land use transitions are dominated by conversions from cropland to forest and impervious surfaces, with transfer intensity increasing over time, forming a heterogeneous pattern characterized by high depletion and high recovery in the upstream, urban expansion in the midstream, and engineering-induced conversion in reservoir areas; land use changes exhibit significant spatial clustering and spillover effects. Cropland reduction and forest expansion are jointly influenced by topographic conditions, locational accessibility, and socioeconomic factors, whereas water body expansion is primarily controlled by engineering regulation, showing weak responses to conventional factors. Under the operation of major water transfer projects, land use/cover changes in the water source area are restructured toward dual objectives of ecological security and engineering guarantee.