Various studies for salinity intrusion in the Vietnamese Mekong Delta (VMD) have been conducted mostly focusing on the lower river mouth without considering the upstream dam impacts. The present paper investigates both the lower and the middle river mouths. Historically, the latter was safer grace to sufficient fresh water from Mekong river basin, which is significantly reduced due to upstream dams’ operations. In addition, climate change as sea level rise also increases the salinity effect on the river mouths of VMD. Therefore, this paper focuses on assessing the combined effects of the upstream dam developments and sea level rise to sustain the safe freshwater condition in both lower and middle river mouths. This study can serve as a basis for the consideration of how to mitigate salinity intrusion impacts and discuss the boundary condition of Chinese Dams’ operations. The results indicated that the salinity control at the VMD is sensitive to the upstream dams’ operations as the modified dam operation scenarios. By increasing the peak discharges during high salinity concentrations from February, the average of maximum salinity concentrations (Smax) and intrusion length (Lsal) in the VMD would reduce by 15.0% and 10.0%, respectively. The combined scenario of flow reduction and sea level rise in the dry season indicated that the average salinity concentration and average intrusion length increased by 45.0 % and 30.0 %, respectively.