Some aspects of habitat seem to enhance the spread of disease whereas others inhibit it. Here, we illustrate and identify mechanisms that connect habitat to epidemiology using a case study of disease in plankton. We see a pronounced relationship between the basin shapes of lakes and fungal (Metschnikowia bicuspidata) disease in the Zooplankton grazer Daphnia dentifera. As we work through seven mechanisms that could explain why Daphnia in some lakes are sicker, we can eliminate some hypotheses (i.e., those relating an index of lake productivity to disease through host density, links between resource quality and transmission rate, and variation in host susceptibility) and find support for others involving food-web actors (e.g., selective predation on infected hosts by fishes, “sloppy predation” by an invertebrate, a possible dilution effect in V-shaped lakes). Furthermore, we identify physical mechanisms (gravity currents, turbulence) that could lead to greater transport of fungal spores to habitat occupied by Daphnia hosts in U-shaped lakes. These results highlight how habitat structure, through its effects on food-web structure and physical processes, can shape wildlife disease.