Concerns continue to mount about the vulnerability of water resources to ongoing changes in the arid region of Central Arizona of southwestern United States. Factors such as population growth, economic development, and environmental concerns compounded by scientific uncertainty associated with climate variability and change are increasing the complexity of water management issues. However, while climate variability and change can contribute to the variations in the supply of water, other local factors can have multifaceted (and sometimes deleterious) effects on water resources. These factors include population growth, practice of water demanding landscape, use of water inefficient technologies, pollutant loading, water dispute along the Colorado River, and the persistence of water-intensive agricultural systems. Given the large degree of uncertainty about climate change and associated variability evaluating sensitivity to other stressors from regional and local levels would be appropriate for assessing societal vulnerability of water resources. Following the weight-of-evidence approach we generated a ranking of various stressors that are exerting pressure on the water resources of the Central Arizona region. We find that that by following modest water demands management practices the region can significantly reduce sensitivity of water resources to ongoing changes. Like wise by adopting simple agronomic practices farmers can also save significant amount of water from agricultural operation. Finding from this research support the argument that development of a more integrated approach that couples social and biophysical factors would provide critical knowledge for improving our understanding of the sensitivity of water resources to future change, and offer insights about future research priorities, as well as policy priorities, aimed at reducing hydrologic vulnerability under an uncertain future climate.