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Understanding the relationship between land use/cover pattern and water quality could provide guidelines for non-point source pollution and facilitate sustainable development. The previous studies mainly relate the land use/cover of the entire region to the water quality at the monitoring sites, but the water quality at monitoring sites did not totally reflect the water environment of the entire basin. In this study, the land use/cover was monitored on Google Earth Engine in Tang-Pu Reservoir basin, China. In order to reflect the water quality of the whole study area, the spatial distribution of the determinants for water quality there, i.e., the total nitrogen and total phosphorus (TN&TP), were simulated by the Soil and Water Assessment Tool (SWAT). The redundancy analysis explored the correlations between land use/cover pattern and simulated TN&TP. The results showed that: (1) From 2009 to 2019, forest was the dominant land cover, and there was little land use/cover change. The landscape fragmentation increased, and the connectivity decreased. (2) About 25% TP concentrations and nearly all the TN concentrations at the monitoring points did not reach drinking water standard, which means nitrogen and phosphorus pollution were the most serious problems. The highest output per unit TN&TP simulated by SWAT were 44.50 kg/hm2 and 9.51 kg/hm2 and occurred in areas with highly fragile landscape patterns. (3) TN&TP correlated positively with cultivated and construction land but negatively with forest. The correlation between forest and TN&TP summited at 500–700-m buffer and construction land at 100-m buffer. As the buffer size increased, the correlation between the cultivated land, and the TN weakened, while the correlation with the TP increased. TN&TP correlated positively with the Shannon’s Diversity Index and negatively with the Contagion Index. This study provides a new perspective for exporting the impact of land use/cover pattern on water quality.