Groundwater is increasingly being overdrafted in the Gulf and Atlantic Coastal regions of the United States. Geochemical data associated with groundwater in these aquifers can provide important information on changes in salinity, recharge, and reaction pathways that can be used to improve water management strategies. Here we evaluated long-term geochemical changes associated with the 23,000 km2 Chicot aquifer system in Louisiana, USA. The Chicot aquifer is currently being overdrafted by about 1,320,000 m3 per day. We compiled selected bulk geochemical data from samples collected from 20 wells in the Chicot aquifer from 1993 to 2015. Oxygen and hydrogen isotope measurements were additionally completed for the 2014 samples. We identified three zones of groundwater with distinctive geochemical character; (1) A groundwater recharge zone in the northern part of the study area with low pH, low salinity, and low temperature relative to other groundwater samples, (2) a groundwater recharge zone in the southeastern part of the study area with low temperature, high alkalinity, and higher Ca and Mg concentrations compared to the other groundwater samples, and (3) groundwater in the southwestern part of the aquifer system with high salinity, high temperature, and a ~1:1 Na/Cl ratio. The geochemistry of these regions has been relatively stable over the last ~20 years. However, in the drought year of 2011, the estimated extent of zones with elevated salinity increased substantially. Geochemical evidence suggests that there was increased infiltration of deeper, more salt-rich waters into the shallower Chicot aquifer.