Surface water quality is greatly affected by regional landscape composition and its spatial configuration. Understanding their relationship can greatly improve the predictability of potential pollution and the evaluation capability of pollutant output. Taking a typical reticulated river network area (Liyang City, Jiangsu Province) as an example, the effects of land use and landscape pattern characteristics on seasonal surface water quality were examined. In this study, 21 water quality indicators were collected from 12 monitoring sections every single month in 2017. Firstly, the characteristics of land use and landscape pattern in multi-scale buffer zones (500, 1000, 1500, 2000, 2500 and 3000 m) were analyzed. Then 12 water quality indexes were identified as the main water quality factors through principal component analysis, and the best impact scale of regional landscape factors on water quality indicators was revealed by redundancy analysis. Finally, partial least squares regression (PLSR) was used to explore the landscape impact on seasonal water quality in the best impact scale. The results showed that 2500 m buffer zone was the best impact scale on water quality indicators. The significance and prediction ability of PLSR models of most water quality indicators were stronger in dry season than that in rainy season. Most water quality indicators in rainy season were significantly affected by orchard land, forest-grass land, dispersion and juxtaposition index (IJI) and Shannon evenness index (SHEI), and these landscape factors were negatively correlated with other water quality parameters except pH and dissolved oxygen (DO). In the dry season, DO, petroleum, chemical oxygen demand, total nitrogen and total phosphorus were most affected by land use. In addition, IJI was the most important impact factor of electrical conductivity, sulfate and nitrite nitrogen, while SHEI had the greatest impact on sulfide and total suspended solids. In addition, landscape metrics had greater impacts on water quality in rainy season. This study revealed the relationship between land use/landscape pattern and seasonal water quality in the reticulated river network area, and provided scientific basis for regional water environment management and landscape pattern optimization.