The Nakdong River is the longest river in South Korea, and flows through various geological terrains with different land use characteristics; therefore, the geochemistry of its water is expected to be influenced by many factors. In this work, the geochemical characteristics of the Nakdong River were examined, and its chemical compositions, δD, δ18O, and δ13CDIC values, and 87Sr/86Sr ratios were determined to investigate the geological and anthropogenic effects on the geochemistry of the Nakdong River water. The obtained concentrations of major ions were strongly affected by both the anthropogenic activity and weathering of the rocks. With increasing the flow distance, the ion concentrations slightly increased; and after the inflow of the Kumho River, which was the largest tributary running through Daegu (the fourth largest city in South Korea), the concentrations of Na and SO4 ions abruptly increased and decreased again, suggesting the existence of strong anthropogenic effects caused by sewage treatment plants and dyeing industrial complex. Other activities such as agricultural ones also increased the NO3 concentration. In July, the high precipitation level from tropical cyclones and downpours decreased the ion concentrations as well as the δD and δ18O values. The δ13CDIC magnitudes showed that the dissolved inorganic carbon mainly originated from mineral weathering upstream, while the oxidation of soil organic materials influenced by agricultural activity became more important downstream. The 87Sr/86Sr ratios revealed that in the upstream regions, the weathering of granite and gneiss complex was dominant, while in the downstream regions, the weathering of sedimentary rocks became more important. The weathering and anthropogenic effects on the river water chemistry were also demonstrated using statistical analysis, which revealed that the water geochemistry was mostly influenced by the anthropogenic sources, including industrial complex, represented by Na, Cl, and SO4. The obtained results show that, as compared to the geochemistry of the Han River (which is also a major river in Korea), the geochemistry of the Nakdong River is more influenced by anthropogenic activities (including agriculture and the industrial complex) due to the different land use.