Strontium and barium to calcium ratios are often used as proxies for tracking animal movement across salinity gradients. Many estuarine rivers face saltwater intrusion due to sea level rise, potentially causing changes in mobility and distribution of these metals upstream. From May 2013 to August 2015, monthly water samples were collected and in-situ measurements were performed at six sites along an estuary strongly affected by saltwater intrusion, the Calcasieu River, with salinity ranging from 0.02 to 29.50 Parts Per Thousand (ppt). Results showed that the total Sr concentration and the Sr/Ca ratio both increased significantly with increasing salinity. The average Sr concentration at the site closest to the Gulf of Mexico (Site 6) was 46.21 µmol/L, about 130 times higher than that of the site furthest upstream (Site 1, 0.35). The average Sr/Ca ratio at Site 6 (8.41 mmol/mol) was about three times the average Sr/Ca ratio at Site 1 (2.89). However, the spatial variation in total Ba concentration was marginal, varying from 0.36 to 0.47 µmol/L. The average Ba/Ca ratio at Site 1 (4.82 mmol/mol) was about 54 times the ratio at Site 6 (0.09), showing a negative relation between the Ba/Ca ratio and salinity. All elemental concentrations and ratios had considerable seasonal variations, with significant differences among sampling months for the Sr and Ba concentrations and the Ba/Ca ratio (p < 0.01). The results suggest that for low-gradient estuarine rivers such as the Calcasieu River, water chemistry upstream would experience substantial Sr and Ca enrichment, potentially affecting aquatic environments and biological communities.