It is widely accepted that characterizing the spatio-temporal trends of water quality parameters and identifying correlated variables with water quality are indispensable for the management and protection of water resources. In this study, cluster analysis was used to classify 56 typical drinking water reservoirs in Zhejiang Province into three groups representing different water quality levels, using data of four water quality parameters for the period 2006–2010. Then, the spatio-temporal trends in water quality were analyzed, assisted by geographic information systems (GIS) technology and statistical analysis. The results indicated that the water quality showed a trend of degradation from southwest to northeast, and the overall water quality level was exacerbated during the study period. Correlation analysis was used to evaluate the relationships between water quality parameters and ten independent variables grouped into four categories (land use, socio-economic factors, geographical features, and reservoir attributes). According to the correlation coefficients, land use and socio-economic indicators were identified as the most significant factors related to reservoir water quality. The results offer insights into the spatio-temporal variations of water quality parameters and factors impacting the water quality of drinking water reservoirs in Zhejiang Province, and they could assist managers in making effective strategies to better protect water resources.