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Soundscape ecology is a relatively new scientific field that uses sound to characterize ecosystems, which can be helpful in tracking species, estimating relative population sizes, and monitoring behavior and overall habitat quality. Estuarine soundscapes are acoustically rich, and sound patterns in these systems are understudied. Therefore, the goal of this study was to understand the soundscape of a deep tidal river estuary, the May River, South Carolina, USA. Acoustic recorders (DSG-Oceans) were deployed to collect sound samples for 2 min every 20 min at 6 stations from February to November 2014. Acoustic data revealed that sound pressure levels (i.e. broadband, low, and high frequency) varied spatially and temporally, exhibiting distinct rhythmic patterns. Acoustic detection rates and diversity of biophonic (e.g. snapping shrimp, fish, and bottlenose dolphins Tursiops truncatus) and anthrophonic sounds (e.g. boat noise) were higher near the river mouth and decreased towards the headwaters. The soundscape exhibited strong temporal patterns of snapping shrimp (genus Alpheus and Synalpheus) snaps, fish calls and choruses (e.g. silver perch Bairdiella chrysoura, black drum Pogonias cromis, oyster toadfish Opsanus tau, spotted seatrout Cynoscion nebulosus, and red drum Sciaenops ocellatus), bottlenose dolphin vocalizations, and vessel noise. Depending upon the species, certain variables (i.e. location, month, day length, lunar phase, day/night, tide, and temperature anomaly) influenced sound production. These data provide new tools and baseline measurements to better understand how soundscapes can be used to gauge habitat quality and impacts of stormwater runoff, climate change, and noise pollution.