Located in the semi-arid and water-scarce area, Comarca Lagunera is one of the main agricultural and dairy products supplying regions in Mexico. As a consequence of the intensive exploitation of groundwater resources for irrigating purposes over one century, the water table has declined up to 200 meters and developed several cones of depression, aggravating the energy consumption necessary for lifting and distributing the groundwater in the agricultural land. Due to this long-term overdraft pumping, not only the groundwater flow dynamics are constantly changing, but also water quality has deteriorated significantly during the last decades. This study evaluates groundwater dynamics and the evolution of ion element composition and the quality of water from the Principal-Lagunera Region aquifer. Elevated nitrate and sulfate concentrations are ubiquitous near Bermejillo in the northwestern portion. Arsenic concentration exceeds international drinking water recommendations in 80% of the sampled sites and reaches maximum values of up to 349 μg/l in agricultural fields. The distribution of these high values of arsenic overlaps with the location of depression cones. This suggests a geogenic origin of this metalloid. Keywords: Aquifer overexploitation, Groundwater chemistry, Arsenic, Comarca Lagunera, Mexico