A previously developed groundwater flow model (https://doi.org/10.3133/sir20185035) was modified and used as the primary tool to assess groundwater availability in the Ozark Plateaus aquifer system which is an important source for municipal, industrial, agricultural, and domestic water supply needs across much of southern Missouri and northern Arkansas, and smaller areas of southeastern Kansas and northeastern Oklahoma. The new model was developed to access changes in simulated hydrologic budget components at the regional scale to quantify hydrologic changes across the Ozark system. The model benefits current and future investigations that involve groundwater-withdrawal scenarios, optimization, particle transport, and monitoring network analysis. Recent short-term drought conditions have emphasized the need to better understand the delicate balance between abundance, sustainability and scarcity. The model also is critical to the ongoing work to quantify groundwater availability in the Ozark aquifer system. The groundwater model simulated 116 years (1900—2016) of historical hydrologic conditions, 45 years (2016-2060) of potential future hydrologic conditions, and the response of the groundwater system to changes in stress. Stress applied to the groundwater system included changes in recharge and increased groundwater withdrawals for water supply. Semi-seasonal stress periods were simulated from the later part of 1991 through 2060 to represent higher demand and lower recharge in the spring and summer months, and lower demand and higher recharge in the fall and winter months. Three scenarios were developed to simulate potential future conditions and assess the potential effects on the hydrologic system and availability of water resources. For each scenario, changes in water levels and hydrologic budget components were evaluated from predevelopment (1900) to present (2016), and 44 years into the future (2060). This USGS data release contains all of the input and output files for the model and the calibration and scenario simulations described in the associated professional paper (https://doi.org/10.3133/pp1854). This data release also includes (1) MODFLOW-NWT (v. 1.1.2) source code, (2) PEST++ source code, and (3) processing Python scripts and associated instruction files for parameter estimation and model calibration using PEST++.