Salinity in irrigation water threatens agricultural productivity as well as the sustainability of cropland around the world. A site in the northeastern Mexicali Valley was chosen to study groundwater quality changes resulting from both natural processes and human activities, including the lining of the All-American Canal with concrete in 2009. Samples were collected from 32 wells in the Mexicali Valley in 2018 and compared to previous datasets obtained from 1981, 1996, and 2008. Multivariate statistical analyses were paired with mapping techniques to better understand the spatial and temporal changes in groundwater quality that have occurred in recent years. The most important processes controlling changes in groundwater quality in the Mexicali Valley were found to be evaporative concentration of salts imported with water from the Colorado River along with water-rock interactions including cation exchange. Infiltration from the All-American Canal, which was an important source of recharge before the canal lining, was found to be of continued importance to farmers in the northern Mexicali Valley in 2018, supplying low-salinity groundwater for the irrigation of salt-sensitive crops. 100% of samples exhibited a high or very high salinity hazard and 9% of samples exhibited a high or very high sodicity hazard, showing that groundwater is not suitable for irrigation under ordinary conditions in much of the Mexicali Valley. The elimination of recharge from the All-American Canal paired with the identified evaporative concentration trends indicate that the use of this low-salinity water is unsustainable. New approaches toward water use efficiency, salinity management, and soil conservation in the Mexicali Valley will need to be taken to maintain crop growth rates and yields into the future.