The Charleston Estuarine System Stock (CESS) of Tamanend’s bottlenose dolphins (Tursiops erebennus) exhibit long-term site fidelity to the Charleston Harbor, and the Ashley, Cooper, and Wando Rivers in Charleston, South Carolina, USA. In the Cooper River, dolphins have been irregularly sighted in upper regions where salinity levels are below what is considered preferred dolphin habitat. We conducted unoccupied aerial system (UAS) surveys in high-salinity (>15 parts per thousand) and low-salinity (<15 parts per thousand) regions (n = 8 sites) of the Cooper River and surrounding waters to assess dolphin distribution in terms presence/absence, detection rate, abundance, and density. We also assessed the influence of ecological factors (salinity, water temperature, season, and prey availability) on dolphin distribution. Dolphins were detected at five sites, with higher salinity and water temperature being significant predictors of presence and abundance. Dolphins were detected year-round across high-salinity sites, and were infrequently detected in low-salinity sites during months with warmer water temperatures. The results from this study contribute to the overall understanding of dolphin distribution across various habitats within the Charleston Estuary System and the potential drivers for their movement into low-salinity waters.