The white shrimp fisheries in South Carolina and Georgia, USA, have undergone substantial reductions in commercial landings over the past few decades. These declines are associated with reduced commercial effort, shifting climate patterns, and disease outbreaks. For example, recent increases in the occurrence of gill melanization, also known as black gill, have led to the suggestion that this epidemic is a major contributor to reduced shrimp abundance in the region. The goal of this study was to assess long-term patterns and drivers of black gill, and its effects on white shrimp abundance, particularly during the fall, when most of the commercial harvest of white shrimp in this region has historically occurred. Data were compiled for fishery-independent (2002–2017) metrics of white shrimp abundance and black gill prevalence from seven estuaries along the South Carolina and Georgia coasts. Phenology of black gill was variable among years, but mean black gill prevalence was significantly related to the Pacific Decadal Oscillation and El Niño–Southern Oscillation climate indices. These analyses show that the prevalence of black gill is sensitive to large-scale fluctuations in climate patterns.