Expanding irrigated agriculture and drought in the Lower Mississippi River Basin have led to large-scale withdrawals of groundwater and a consequent decline in the Mississippi River Valley Alluvial Aquifer. Conserving the aquifer, while at the same time providing for economic growth, is a challenge for policy makers. We develop a spatially explicit landscape level model for analyzing the aquifer and economic consequences of alternative crop mix patterns. The spatially explicit aquifer model incorporates irrigation needs of the crops grown, initial aquifer thickness, hydro-conductivity of the aquifer, and distance to surrounding grid cells to predict the proportion of groundwater removed from surrounding cells due to pumping on each grid cell. The spatially explicit economic model incorporates site characteristics and location to predict economic returns for a variety of potential crop types. By thinking carefully about the arrangement of activities, we find crop mix patterns that sustain high levels of the aquifer and economic returns. Compared to the crop mix of the current landscape, we show that both aquifer conservation and the value of economic activity could be increased substantially.