Water quality is highly influenced by the composition and configuration of landscape structure, and regulated by various spatiotemporal factors. Using the Wujiang river watershed as a case study, this research assesses the influence of landscape metrics-including composition and spatial configuration-on river water quality. An understanding of the relationship between landscape metrics and water quality can be used to improve water contamination predictability and provide restoration and management strategies. For this study, eight water quality variables were collected from 32 sampling sites from 2014 through 2017. Water quality variables included nutrient pollutant indicators ammoniacal nitrogen (NH 3 -N), nitrogen (NO 3 − ), and total phosphate (TP), as well as oxygen-consuming organic matter indicators COD (chemical oxygen demand), biochemical oxygen demand (BOD 5 ), dissolved oxygen (DO), and potassium permanganate index (COD Mn ). Partial least squares (PLS) regression was used to quantitatively analyze the influence of landscape metrics on water quality at five buffer zone scales (extending 3, 6, 9, 12, and 15 km from the sample site) in the Wujiang river watershed. Results revealed that water quality is affected by landscape composition, landscape configuration, and precipitation. During the dry season, landscape metrics at both landscape and class levels predicted organic matter at the five buffer zone scales. During the wet season, only class-level landscape metrics predicted water contaminants, including organic matter and nutrients, at the middle three of five buffer scales. We identified the following important indicators of water quality degradation: percent of landscape, edge density, and aggregation index for built-up land; aggregation index for water; CONTAGION; COHESION; and landscape shape index. These results suggest that pollution can be mitigated by reducing natural landscape composition fragmentation, increasing the connectedness of region rivers, and minimizing human disturbance of landscape structures in the watershed area.