BackgroundWater insecurity is linked to depression in low- and middle-income countries (LMICs), though it remains unclear how geospatial clustering of water insecurity in rural regions is associated with risk for depression.MethodsWe conducted a population-based survey of a rural parish in southwestern Uganda (N = 1603) to evaluate the joint geospatial clustering of water insecurity and risk for depression among men and women living in rural Uganda.ResultsGeospatial clustering of self-reported water insecurity and depressive symptoms was found to be present among both men and women. Depression hotspots were more often observed near water insecurity hotspots among women, relative to men. Multivariable regression revealed that residing in a water insecurity hotspot significantly increased risk for depressive symptoms among women, but not among men.ConclusionsResiding in a water insecurity hotspot is associated with greater risk for probable depression among women, but not among men, pointing to the need for focused depression screening among women residing in water insecure households.