Water pollution originating from land use and land cover (LULC) can disrupt river ecosystems, posing a threat to public health, safety, and socioeconomic sustainability. Although the interactions between terrestrial and aquatic systems have been investigated for decades, the scale at which land use practices, whether in the entire basin or separately in parts, significantly impact water quality still needs to be determined. In this research, we used multitemporal data (field measurements, Sentinel 2 images, and elevation data) to investigate how the LULC composition in the catchment area (CA) of each water pollution measurement station located in the river course of the Los Perros Basin affects water pollution indicators (WPIs). We examined whether the CAs form a sequential runoff aggregation system for certain pollutants from the highest to the lowest part of the basin. Our research applied statistical (correlation, time series analysis, and canonical correspondence analysis) and geo-visual analyses to identify relationships at the CA level between satellite-based LULC composition and WPI concentrations. We observed that pollutants such as nitrogen, phosphorus, coliforms, and water temperature form a sequential runoff aggregation system from the highest to the lowest part of the basin. We concluded that the observed decrease in natural cover and increase in built-up and agricultural cover in the upper CAs of the study basin between the study period (2016 to 2020) are related to elevated WPI values for suspended solids and coliforms, which exceeded the allowed limits on all CAs and measured dates.