Extreme droughts are increasing in frequency, severity, and duration in arid and semi-arid regions around the world due to climate change. As a result, plant species that are typically capable of withstanding regular drought stress are exposed to conditions outside of their normal range, rendering them susceptible to opportunistic disease-causing agents. Theoretical frameworks describing the roles of environmental and biotic stressors in driving plant mortality are well established. However, there is a lack of empirical data with which to resolve how these factors interact in vivo. Furthermore, studies that document progression of stress and dieback throughout the course of a multi-year drought event in situ are rare. In this dissertation, I detail a series of studies aimed at understanding mechanisms of dieback and mortality by focusing on a severe canopy dieback event in a classically drought tolerant chaparral shrub, big berry manzanita (Arctostaphylos glauca) in Santa Barbara, California, during an historic California drought. I provide strong evidence that dieback is caused by members of the fungal Botryosphaeriaceae (Bot.) family in conjunction with extreme drought, and that dieback is also related to increased drought stress along an elevational gradient. By conducting a field survey, I identify Neofusiccocum australe as the most prevalent and widely distributed fungal pathogen in A. glauca., and that dieback is strongly correlated with Bot. infection. Using a full-factorial design in a greenhouse experiment, I provide evidence that extreme drought and infection by N. australe can indeed act synergistically, together driving faster and greater mortality in young (approx. one-year-old) A. glauca than either factor alone. Lastly, by taking measurements on water availability, dark-adapted leaf fluorescence, and photosynthesis in A. glauca shrubs across an elevational gradient, I provide evidence that landscape-level factors can contribute to localized variability in water stress and canopy dieback severity in A. glauca, and may be useful in predicting vulnerabilities during future drought. Remarkably, no new mortality was observed throughout the study, suggesting extreme resiliency in adult shrubs. However, canopy dieback alone can impact wildlife and fuel loads, even when not associated with mortality. Together, these results provide strong evidence that A. glauca dieback was caused synergistic effects between extreme drought and infection by N. australe, and that lower elevations and exposed slopes may be at greatest risk for future events.