Functions of inland, freshwater depressional wetlands of the Great Plains are driven by natural disturbance in the form of fluctuating water levels or shifts between wet and dry ecological states. The geographically isolated prairie potholes and playas form broad-scale systems or networks that support biodiversity and provide ecological goods and services. Anthropogenic disturbance, primarily in the form of sediment accretion, results in the functional loss of individual wetlands from the system. The ecological value of individual depressional wetlands has been documented, but there has not been any assessment of the contribution of individual wetlands to the system. Network analysis can be used to prioritize the contribution of individual wetlands to the system for the purpose of conservation and management. We utilized the playas wetland system of the Southern High Plains to illustrate this concept. Playas form a redundant, resilient network based on natural disturbance (i.e., inundation patterns) across broad spatial and temporal scales that support biodiversity. Loss of individual playas to sediment accretion is causing the network to break down, resulting in the need for a greater proportion of inundated playas to provide the original level of ecological goods and services. The effects of decreased functional connectivity due to anthropogenic disturbance at the system scale portend negative effects on movement strategies, dynamics and persistence of local populations, decreased biodiversity, and, ultimately, the redistribution and system-wide extinction of playa wetland-dependent populations and loss of associated functions.