Low-order streams located near urban areas usually receive domestic, industrial, and agricultural wastewaters that negatively affect river water quality. Additionally, water pollution is associated with land-use variations around the river, which is characterized by unplanned urbanization, intense agricultural activities, and deforestation. This work correlated land-use patterns with physicochemical quality and genotoxic potential of water at four points (P1 to P4) along the Extrema River, located in an industrial and agricultural area of Central Brazil. Physicochemical analyses indicated that the water collected from the Extrema River is inappropriate for human consumption. Using the Allium cepa model, no evidence of cytotoxicity was observed at any point; in contrast, the genotoxic potential of these water samples was observed. The correlation of these results with land use showed that the water collected at P3 was the most contaminated; this is probably due to the inflow of wastewater from municipal, industrial, and agriculture activities. Different results were observed for P2 and P4, where land-use analysis attributed the water quality to forest burns. We concluded that differential use of the land changed the characteristics of the associated river water, and A. cepa parameters were more related to land-use characteristics than to physicochemical parameters. This study highlighted the importance of associating land use with the cyto genotoxic potential of water.