Water quality of rivers is strongly influenced by landscape characteristics of their watershed, including land use /cover types, and their spatial configuration. This research evaluates the effects of land cover changes on the water quality of the Zayandehroud River, which is the most important river in the center of Iran. The main goal of this study was to quantify the change in rangelands, forests, and bare lands in the Zayandehroud river basin, which suffered intense human interference, in a period of 11 years (1997–2008), and to evaluate how landscape patterns (including the number of patches, edge density, percentage of rangelands, forests, and bare lands) influence on the 14 water quality indices (including BOD5, EC, NO3, P, and TDS) measured in 10 stations along the river. Results showed that from 1997 to 2008, bare lands increased from 5.8 to 20 %, while rangelands decreased from 70 to 55 % in the whole basin. The results indicated that water quality was significantly correlated with both the proportions and configuration of rangeland and bare land areas. The total edge (TE) of rangeland area had positive effects on water quality, especially on BOD5 and EC. Percentage of landscape (PLAND) and largest patch index (LPI) metrics of rangeland had positive effect on decreasing nutrient (NO3, PO4). The results showed that water quality was more likely degraded when there was high edge density (ED) of bare lands. Results of this study also revealed that degradation of rangeland lead to the degradation of water quality. Finding of this study highlights the importance of rangeland conservation in water quality management at landscape scale.