The Charleston Harbor in South Carolina (SC)is a major port that experiences high levels of vessel traffic. Historical analyses of coastal bottlenose dolphin (Tursiops truncatus, now Tursiops erebennus) sightings identified multiple core use areas in the harbor that overlap with these anthropogenic activities. Informed by these long-term spatial data, passive acoustic monitoring, visual surveys, and prey sampling were conducted from December 2017 to June 2019 to assess the relationships and multivariate interactions that may influence dolphin vocalization patterns. Vocalizations varied spatially and temporally, peaking in fall and winter months coinciding with decreases in water temperature and daylight hours, following patterns previously reported in other SC estuaries. Dolphin prey and total fish abundance decreased with water temperature, which may indicate that dolphins echolocate and whistle more frequently in the winter months when prey are scarce and sound-producing species are less soniferous. Dolphin sightings and vocalizations were highly correlated. Dolphin occurrence was highest in the areas surrounding the confluence of the Cooper and Wando Rivers, along the shipping channel, where vessel and sound-producing fish detections were greatest. When vessel noise occurred, dolphins increased their vocalizations, which suggests that this population may be modifying its acoustic repertoire in response to increased noise levels. Multivariate interactions indicate strong spatial and seasonal patterns in vocalization rates that may be associated with dolphin and prey abundance as well as noise-induced redundancy.