The Takelsa phreatic aquifer (Northeastern Tunisia) is an important source of fresh water for different economic sectors in the region that are strongly dependent on groundwater resources but, the aquifer is showing increasing signs of groundwater quality degradation like many other regions in the Mediterranean Basin. By integrating geochemical and multivariate statistical investigation methods, this research aims to identify the main geochemical processes and anthropogenic activities that are responsible for regional groundwater quality evolution, identifying the origins of salinity and nutrients, and their implications for groundwater use forcropirrigation and drinking water supply in order to improve aquifer management practices. The results show that groundwater facies vary from Ca-Mg-SO to Na-Cl water type and that mineralization is strongly controlled by mineral dissolution and cation exchange. The isotopic analyses indicate that groundwater is recharged by rainwater infiltration at higher altitudes and that a cumulative evaporative effect may contribute to local increase of salt content in groundwater. The Water Quality Index (WQI) used to determine the suitability of the Takelsa groundwater for drinking purposes reveals that just half of the groundwater points sampled show good to excellent quality for human consumption. The groundwater quality is also limited for irrigation purposes due to anthropogenic activities existing throughout the region. As groundwater in the studied region is crucial for irrigation and human supply, the identified groundwater quality problems and the identification of the main processes responsible for them should contribute to improve the infrastructure and managementpractices to allow the region to sustainable exploit the available groundwater resources.