87Sr/86Sr of river water are of great significance in constraining oceanic strontium (Sr) record and terrestrial climate change due to the connection of continental weathering and the adjacent ocean. This work presents the geochemical characteristics of dissolved Sr and hydrochemistry, and estimates chemical weathering rate together with elemental Sr flux during the flood season of the Mun River, the largest tributary of Mekong River. Hydrochemistry analysis indicates the dominance of Cl− and HCO3− for major anions with the average of 34.6 and 43.0 mg/L, respectively, and Na+ and Ca2+ together dominated the cationic composition with the average of 22.9 and 10.5 mg/L, respectively. The ion concentrations during flood season were lower than that in dry season, implying tremendous river runoff due to extreme rainfall. The dissolved Sr ranges 6.1–237.5 μg/L with higher contents in the upper Mun. Sr contents in flood season are lower and less fluctuated than that in dry season, whereas the divergence between up and downstream becomes larger. 87Sr/86Sr ranges 0.7100–0.7597, slightly higher than global average. Elemental molar ratio analysis partly corroborates the inference from correlation analysis, but 87Sr/86Sr does not correlate with Na/Ca, indicating additional influence except for the weathering of evaporites and silicates. Comparing to regional wastewater and rainwater, the lower reaches exhibits superimposed impact of agricultural inputs on weathering to dissolved loads, especially in downstream with more tributary convergence. Extreme rainfall during flood season and extensive agricultural production activities may interfere in altering riverine solutes. Silicate weathering rate and CO2 consumption rate are calculated as well as the yearly 87Sr in excess to the Mekong River and finally to the Pacific Ocean with a Sr flux of 1.98 × 103 tons/year, indicating significant influence on seawater strontium isotope evolution in the long run. Together with tropical climate and high-intensity precipitation, the accelerated chemical weathering process seems inevitable. Therefore, the impact of agricultural interference in the pan-Mekong River basin needs more systematic and multi-angle research to provide a comprehensive insight on better watershed management under tropical climatic conditions.