Grasslands are highly imperiled as a result of widespread conversion for agriculture and alteration from human development. Remaining grasslands are susceptible to mismanagement, development and fragmentation, and variable weather associated with global climate change. Understanding the response of declining grassland species to these challenges will be important for informed conservation and management. We assessed Greater Prairie-Chicken (Tympanuchus cupido) survival and nest site selection in tallgrass prairie characterized by interacting fire and grazing disturbance and oil and gas infrastructure. We found that Greater Prairie-Chicken survival was most affected by weather variability (expressed in our models as solar radiation) while most other variables had little influence. Focal disturbance did not affect survival directly, but vegetation height, which is greatly influenced by fire and grazing processes, was positively associated with nest survival. Greater Prairie-Chickens chose nesting locations that maximized time post fire while minimizing tree cover and distance to leks. Future conservation efforts for Greater Prairie-Chickens should focus on variable fire regimens that create areas of residual biomass to increase vegetation height and potentially reduce the effects of solar radiation while decreasing woody vegetation that is avoided by nesting females. However, even the best management practices may prove to be futile in the southern Great Plains if climate change continues to create unfavorable nest survival conditions. Management that creates and maintains suitable nesting sites through the use of interacting fire and grazing should maximize the potential for high reproduction in years when local weather variables are favorable.