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This paper uses Visual MODFLOW to simulate potential impacts of anthropogenic pumping and recharge variability on an alluvial aquifer in semi-arid northwestern Oklahoma. Groundwater withdrawal from the aquifer is projected to increase by more than 50% (relative to 1990) by the year 2050. In contrast, climate projections indicate declining regional precipitation over the next several decades, creating a potential problem of demand and supply. The following scenarios were simulated: (1) projected groundwater withdrawal, (2) a severe drought, (3) a prolonged wet period, and (4) a human adjustment scenario, which assumes future improvements in water conservation measures. Results indicate that the combined impacts of anthropogenic pumping and droughts would create drawdown of greater than 12 m in the aquifer. Spatially, however, areas of severe drawdown will be localized around large-capacity well clusters. The worst impacts of both pumping and droughts will be on stream-aquifer interaction. For example, the projected aquifer pumpage would lead to a total streamflow loss of 40%, creating losing stream system regionally. Similarly, a severe drought would lead to a total streamflow loss of >80%. A post-audit of the model was also carried out to evaluate model performance. By simulating various stress scenarios on the alluvial aquifer, this study provides important information for evaluating management options for alluvial aquifers.