AbstractConservation plans designed to sustain North American duck populations prominently feature a key hypothesis stating that the amount of the landscape in perennial cover surrounding upland duck nests positively influences nest survival rates. Recent conflicting research testing this hypothesis creates ambiguity regarding which management actions to pursue and where to prioritize conservation delivery. We compared existing models and new formulations of existing models explaining spatiotemporal variation in nest survival using independent data documenting the fate of >20,000 duck nests within the Drift Prairie, Missouri Coteau, and Prairie Coteau physiographic regions of the United States Prairie Pothole Region during 2002–2018. Our results suggest an inconsistent relationship between perennial cover and survival of upland duck nests, which depended upon physiographic region and current and time‐lagged landscape and environmental conditions. The magnitude and direction of how perennial cover correlated with daily nest survival depended on its dominance as a landcover type. A positive relationship existed when perennial cover was a minor component of landcover in all physiographic regions (<30% of a 10.4‐km2 area) and, in the Drift Prairie and Prairie Coteau, when perennial cover was the dominant landcover type (>60%). A constant or negative relationship was predicted at locations of about 30–60% perennial cover. Additionally, environmental conditions (i.e., density of wetlands and estimated gross primary productivity in the previous year) moderated or enhanced the effect of perennial cover on nest survival, depending on physiographic region. Our finding of inconsistency in the relationship between perennial cover and nest survival contradicts the conservation premise that nest survival universally increases linearly when uplands are converted to perennial cover. Promoting policies and management actions designed to increase perennial cover can be expected to be situationally but not consistently associated with higher survival of upland duck nests.