Agricultural intensification and urban sprawl have led to significant alterations in riverscapes, and one of the critical consequences is the deterioration of water quality with significant implications for public health. Therefore, the objectives of this study were the assessment of the water quality of the Suquía River, the assessment of LULC change at different spatial scales, and the analysis of the potential seasonal correlation among LULC change and Water Quality Index (WQI). The Sample Sites (SS) 1 and 2 before Cordoba city had the highest WQI values while from SS3 the WQI decreased, with the lowest WQI close to the wastewater treatment plant (SS7) after Cordoba city. From SS8 in a agricultural context, the WQI increases but does not reach the original values. In light of analysis carried out, the correlation between water quality variables and the different LULC classes at the local and regional scales demonstrated that WQI is negatively affected by agricultural and urban activities, while natural classes impacted positively. The spatialization of the results can help strongly in assessing and managing the diffusion of point and non-point pollution along the riverscape. The knowledge gained from this research can play a crucial role in water resources management, which supports the provision of river ecosystem services essential for the well-being of local populations.