Groundwater is the main source for domestic drinking water supply, irrigation, and industrial activities in Zacatecas in central Mexico, a good example for numerous semiarid regions worldwide, however, there is insufficient information about characterization and evolution of the baseline water quality to create hydrogeological conceptual models, fundamentals for the future planning of new sources of groundwater supply for the population, especially under ongoing global climate change conditions. By a multi-method analysis that included geological, geophysical, hydrochemical and isotopic tools this investigation allowed the identification of: a) local flows, represented by shallow groundwater and shallow wells, hosted over basin fill sediments with low average temperatures (≈ 23.3 °C), variation in water types related to anthropogenic activities, low trace elements concentrations, δ18O and δ2H signatures indicating surface water and tritium being present in this system, b) intermediate flows (25 °C), identified in wells with depths of 100 to 200 m, water circulating through the basin fill sediments and the sequence of volcanic rocks characterized by intermediate concentrations of trace elements, and groundwater ages calculated for this system vary from 1,000 to 6,000 years, c) regional flows in volcanic rocks, characterized by groundwater from wells with depths of more than 200 m, high temperatures (up to 31.5 °C) and elevated concentrations of trace elements. The δ18O and δ2H signals are more homogenous and the 14C residence times for this flow system are greater than 8,000 years, and d) regional flows in Cretaceous rocks, with depths greater than 400 m, the highest temperatures (≈ 43.7 °C) and intermediate concentrations of trace elements. The δ18O and δ2H signals are homogenous and δ13C can widely be associated with carbonate shales. The hydrogeochemical evolution has been documented along a 62 km flow line to develop a robust conceptual model, reflecting the water–rock interaction in the system. Physicochemical parameters, as well as major and trace element concentrations, reflect a distinct evolution according to the flow paths and their increase is generally proportional to the residence time. Likewise, processes of dissolution of feldspars and some clay minerals from initial weathering in the basin fill sediments, as well as devitrification of the glassy matrix in the volcanic rocks are taking place in the evolution of the system.The results obtained through the analysis of water–rock interaction in this research can be applied to other semi-arid regions with geogenically impacted aquifers, due to the geological and climatic similarity with numerous volcano-sedimentary basins around the world.