Salinity intrusion is a pressing issue in the coastal areas worldwide. It affects the natural environment and causes massive economic loss due to its impacts on the agricultural productivity and food safety. Here, we assessed the salinity intrusion in the Tra Vinh Province, in the Mekong Delta of Vietnam. Landsat 8 OLI image was utilized to derive indices for soil salinity estimate including the single bands, Vegetation Soil Salinity Index (VSSI), Soil Adjusted Vegetation Index (SAVI), Normalized Difference Vegetation Index (NDVI), and Normalized Difference Salinity Index (NDSI). Statistical analysis between the electrical conductivity (EC1:5, dS/m) and the environmental indices derived from Landsat 8 OLI image was performed. Results indicated that spectral values of near-infrared (NIR) band and VSSI were better correlated with EC1:5 (r2 = 0.8 and r2 = 0.7, respectively) than the other indices. Comparative results show that soil salinity derived from Landsat 8 was consistent with in situ data with coefficient of determination, R2 = 0.89 and RMSE = 0.96 dS/m for NIR band and R2 = 0.77 and RMSE = 1.27 dS/m for VSSI index. Findings of this study demonstrate that Landsat 8 OLI images reveal a high potential for spatiotemporally monitoring the magnitude of soil salinity at the top soil layer. Outcomes of this study are useful for agricultural activities, planners, and farmers by mapping the soil salinity contamination for better selection of accomodating crop types to reduce economical loss in the context of climate change. Our proposed method that estimates soil salinity using satellite-derived variables can be potentially useful as a fast-approach to detect the soil salinity in the other regions with low cost and considerable accuracy.