Ecotourism on private lands may be an incentive for conservation because of potential profits to landowners. Conservation planners in southern Africa have posited that ecotourism has higher potential in drier regions where agricultural profit is lower, and this hypothesis would seem to apply to the Great Plains of North America, which has a gradient of precipitation. Row crop agriculture is a strong competitor for land use in the eastern Great Plains. Rangelands are more common in the western Great Plains, and cattle grazing on grasslands is compatible with ecotourism. To support current interest in ecotourism in the Great Plains, we developed a spatial model to predict potential for ecotourism by overlaying a map of annual precipitation levels with a spatial tourism model developed by evaluating distance to cities and interstate highways as well as to existing ecotourism destinations. Our model suggests that northern and western portions of the Great Plains have the highest potential for ecotourism ventures that cater to short-term sightseeing visitors, while three areas in the northern and central Plains have high potential for ecotourism ventures providing long-term nature-seeking experiences in unique landscapes. The identification of an ecotourism audience is critical for success, and our spatial analysis has potential to support ecotourism and conservation of prairies and wildlife in the Great Plains.