The objective of this study was to develop and calibrate a groundwater model for a 4-county area in the Texas High Plains of the Ogallala Aquifer Region. This study is a major component of a comprehensive regional analysis of groundwater depletion in the Ogallala Aquifer Region with the purpose of understanding short- and long-term effects of existing and alternative land use scenarios on groundwater changes. A comprehensive geographic information system (GIS) database was developed for this purpose that included a recent land cover map. This 2008 land cover map was developed using Landsat satellite imagery with ground-truth points for Dallam, Sherman, Hartley, and Moore Counties in Texas. Other GIS layers included aquifer elevation contours, surficial geology, hydraulic conductivity contours, saturated thickness areas, well locations and piezometric heads, aquifer discharge and recharge areas, topography, hydrographic data, ecological regions, and soil type data. The hydrologic simulations were done using MODFLOW. Anticipated outcomes from this modeling effort include the effect of change in land use/land cover on sustainability of the aquifer life in the study region. Our results will be used to develop strategies to conserve groundwater in the Ogallala Aquifer beneath Central High Plains and improve regional water planning.