Calera Aquifer is the main source of water for irrigated agriculture, industrial and drinking water purposes in the Calera Aquifer Region (CAR) in the State of Zacatecas, Mexico. Irrigated agriculture accounts for 80% of total groundwater extracted from the Calera Aquifer. Limited rainfall and low agricultural water use efficiency in combination with fast growing industrial and urban water demand are contributing to groundwater depletion at an unsustainable rate. The main objective of this study was to develop and evaluate a groundwater modeling system using MODFLOW-2000 for the CAR. Predicted groundwater levels were compared with measured data collected from observation wells between 1954 and 2004. Performance statistics indicated that the model performed well in simulating historic groundwater levels in the central part of the CAR where irrigated agriculture is concentrated. However, further improvements in the conceptual model may be needed to improve predictions in other parts of the CAR.