Studies in water quality management have indicated significant relationships between land use/land cover (LULC) variables and water quality parameters. Thus, understanding this linkage is essential in protecting and developing water resources. This article extends the conventional geographical weighted regression (GWR) to a temporal version in order to take both spatial and temporal variations of such linkages into account, which has been ignored by many of the previous efforts. The approach has been evaluated for total nitrates and nitrites' concentration as the case study. For this, observations of 45 water quality sampling stations were examined in a time interval of 20 years (1992–2011), and the linkages between LULC variables and NO2 + NO3 concentration were extracted through Pearson correlation coefficient as a global regression model, the conventional geographic weighted regression, and the proposed spatio-temporal weighted regression (STWR). Comparing the results based on two global criteria of goodness-of-fitness (R2) and residual sum of squares (RSS) verifies that the simultaneous consideration of spatial and temporal variations by STWR substantially improves the results.