In this study, remote sensing and geographic information systems were used to assess the influence of land cover characteristics on the water quality of the El Guájaro reservoir, in northern Colombia. The water quality data were acquired during three measurement and sampling campaigns (2013, 2015 and 2016), complemented with data obtained by the regional environmental authority. The status of land cover in the basin of the El Guájaro reservoir was assessed by calculating the Normalized Difference Vegetation Index (NDVI), Normalized Difference Moisture Index (NDMI) indicators and land cover classification, using Landsat-8 surface reflectance images obtained from the Google Earth Engine platform. The analysis of the interaction between vegetation cover and water quality was based on Pearson correlations and Principal Component Analysis (PCA). The correlation analysis indicated significant correlations of NDVI with temperature (r = 0.47), DO (r = − 0.64), pH (r = − 0.37), general vegetation (r = 0.83), urban areas (r = 0.56), bare soil (r = − 0.86), and nutrients (r = − 0.92 and r = − 0.82, for NO3 and PO4 respectively); and NDMI with temperature (r = 0.46), DO (r = − 0.64), TSS (r = − 0.33), general vegetation (r = 0.87), urban areas (r = 0.61), bare soil (r = − 0.89), water areas (r = − 0.40), and nutrients (r = − 0.93 and r = − 0.83, for NO3 and PO4 respectively). Additionally, it was observed that land covers corresponding to urban areas and bare soil affects the water quality of the reservoir. The results displayed strong correlation and association between vegetation cover conditions, which are affected by the various agricultural activities that take place in the basin, and the water quality of the reservoir.