This study quantitatively explored the driving mechanisms of various factors on the changes in lake water quality indicators based on the meteorological, land use, and water quality monitoring data of the Ulansuhai Lake Basin from 2000 to 2022, by adopting the generalized additive model, econometric model, and hybrid evolutionary algorithm. Meanwhile, the contribution rates of different factors were measured via grey relational analysis. The results showed that:changes in land use patterns of the basin were the primary driving factor for the variations in water quality of Ulansuhai Lake; the expansion of cultivated land, grassland, and impervious surfaces significantly deteriorated the water quality, whereas the increase in forestland, water bodies, and bare land areas contributed to water quality improvement. Changes in the aquatic environment exerted the second most significant impact on lake water quality；factors including water electrical conductivity, transparency, water depth, pH value, dissolved oxygen(DO), and chemical oxygen demand (COD) exhibited nonlinear relationships with total nitrogen (TN) and total phosphorus (TP) concentrations. Climatic factors had a relatively minor influence on water quality; the rise in annual average temperature increased the COD content, while the growth in annual precipitation reduced the TP mass concentration. Water quality changes of Ulansuhai Lake were affected by the combined effects of multiple factors, among which human activities (changes in land use patterns) exerted a more pronounced impact than climatic factors.