Based on measured data of Taihu Lake from 2005 to 2022, the Mann-Kendall test and BP neural network model were used to analyze the interannual variation characteristics of chlorophyll-a mass concentration and its synergistic response to hydrodynamic factors (water level, wind speed, precipitation), nutrient factors (total nitrogen, total phosphorus, CODMn), and thermal factors (air temperature, daylight duration, total radiation). The results show that the chlorophyll-a mass concentration has shown an upward trend since 2005, with the average mass concentration from 2015 to 2022 being about 95% higher than that from 2005 to 2014. However, the peak mass concentration of chlorophyll-a has exhibited a declining trend since 2020. The variation process of chlorophyll-a mass concentration shows the highest sensitivity to the synergistic effects of total radiation, water level, and air temperature. The thermal factors have the most significant impact on the variation process of chlorophyll-a mass concentration.