Groundwater salinization is a major threat to the water supply in coastal and arid areas, a threat that is expected to worsen by increased groundwater withdrawals and by global warming. Groundwater quality in Central Mexico may be at risk of salinization due to its arid climate and since groundwater is the primary source for drinking and agriculture water. Only a handful of studies on groundwater salinization have been reported for this region, most constrained to a small area and without trend analyses. To determine the extent of salinization, total dissolved solids (TDS), sodium (Na+), nitrate as nitrogen (NO3-N) and sodium adsorption ratio (SAR) are commonly used. Available water quality data for about 200 wells, sampled annually between 2012 and 2021, were used to map the spatial distribution of NO3-N, TDS, Na+, and SAR. Upward trends and Spearman correlation were also determined. The study area was subdivided into three sections to estimate the impact of climate and lithologies on groundwater salinity. The results showed that human activities (agriculture) and dissolution of carbonate and evaporite rocks were major sources of salinity, and evaporation an enriching factor. Temporal trends occurred in only a few (about 7%) wells, primarily in NO3-N. The water quality for irrigation was generally good, (SAR < 10 in 95% of samples); however, eight wells contained water hazardous to soil (TDS > 1750 mg L−1 and SAR > 9). The results detected one aquifer with consistently high concentrations and upward trends and eight lesser impacted aquifers. Identifying the wells with upward trends is important in narrowing down the possible causes of their concentration increase with time and to develop strategies that will infuse sustainability to groundwater management.