Water availability is becoming more uncertain as human populations grow, cities expand into rural regions and the climate changes. In this study, we examine the functional relationship between water use and the spatial patterns of developed land across the rapidly growing region of the southeastern United States. We quantified the spatial pattern of developed land within census tract boundaries, including multiple metrics of density and configuration. Through non-spatial and spatial regression approaches we examined relationships and spatial dependencies between the spatial pattern metrics, socio-economic and environmental variables and two water use variables: a) domestic water use, and b) total development-related water use (a combination of public supply, domestic self-supply and industrial self-supply). Metrics describing the spatial patterns of development had the highest measure of relative importance (accounting for 53% of model's explanatory power), explaining significantly more variance in water use compared to socio-economic or environmental variables commonly used to estimate water use. Integrating metrics characterizing the spatial pattern of development into water use models is likely to increase their utility and could facilitate water-efficient land use planning.