Understanding the link between land use/land cover (LULC) patterns and water quality can establish guidelines for non-point source pollution management and sustainable development. The transboundary Shatt Al-Arab river basin (Iraq-Iran) suffers from nutrient pollution problems. This study aimed to estimate flow volume, nitrogen, and phosphorus pollution in this basin and how such pollution relates to LULC and flow volume using the Soil and Water Assessment Tool (SWAT) model. The data used in the SWAT model were the Digital Elevation Model (DEM), slope, parent materials of soil, LULC, and weather data (i.e., precipitation, relative humidity, temperature, solar radiation, and wind speed). The results showed that from 2004 to 2021, the annual Total Nitrogen (TN) and Total Phosphorus (TP) outputs were 618 and 140 kg km−2, respectively. The TN discharge load ranged from 27 to 6500 kg km−2 yr−1, while the TP discharge load ranged from 1 to 1600 kg km−2 yr−1. Redundancy Analysis (RDA) revealed that cropland and urban cover ratios were positively correlated with the annual TN and TP discharge loads. On the contrary, shrubland and bare land ratios were negatively correlated with the annual TN and TP discharge loads. Results showed that flow volume is positively correlated with precipitation. Both annual TN and TP discharge loads exhibited a positive correlation with flow volume and a negative correlation with subbasin area. The highest annual TN and TP discharge loads were in the middle parts of the basin, where the cultivated land and construction land are concentrated and the flow volume is high. Thus, findings suggest that the basin is sensitive to shifts in flow volume associated with global climate change and to shifts in LULC change. No study for nutrient discharge load assessment for the entire Shatt Al-Arab river basin has been performed before. Hence, the novel contribution of this study will guide the hydrologists and water resource planners in the basin to establish effective water policies, climate change mitigation strategies, and environmental change adaptation strategies.