The Prairie Pothole Region (PPR) is the primary breeding region for most species of North American dabbling ducks (Anas spp.). Conservation of these species is guided in part by knowledge of relationships between nest survival probability and habitat features. Positive relationships between duck nest survival and amount and configuration of herbaceous perennial vegetation have been observed in previous studies, but these 2- to 4-year studies might not have adequately characterized the temporal effect of wet–dry episodes on nest survival. Over an eight-year period, we studied nest survival of five species of ducks in the PPR relative to spatial and temporal variation in pond density, primary productivity, and hydrologic status of wetlands, soil, and vegetation on 52 study sites selected to span a gradient of spatial variation in proportion of herbaceous perennial vegetation and in number of wetland basins. We observed the fate of 12 754 nests. Consistent with past studies, 90% of nests that failed to hatch were destroyed by predators. Nest survival probability was positively related to current-year pond density and primary productivity, negatively related to pond density and primary productivity during the previous two years, and positively related to the number of wetland basins on the study site. Predicted relationships between nest survival and proportion or configuration of herbaceous perennial vegetation in the surrounding landscape were not supported. For mallard (Anas platyrhynchos), median estimated nest survival probability ranged from 0.02 (SE = 0.01) to 0.22 (SE = 0.02). Estimated nest survival was greatest on sites with numerous wetland basins that had transitioned from dry, unproductive conditions to wet, productive conditions in the previous 1–2 years. Our results were consistent with time-lagged responses of food webs to resource pulses in a broad array of ecosystems. Our study highlighted the importance of wetland basins and wet–dry episodes to duck nest survival in the PPR. Current habitat conservation efforts focus on landscapes with numerous wetland basins and a high proportion of herbaceous perennial vegetation. Our results suggest that future conservation efforts should focus on preserving high-density wetland complexes across as large a geographic extent as possible even in cropland-dominated landscapes.