Vibrio spp. are naturally occurring bacteria in marine and estuarine environments around the world. The genus includes several human and animal pathogens that can negatively impact human health, seafood and aquaculture. Vibrio spp. populations are capable of rapid adaptation in response to changing environmental conditions, making them dynamic over short-term and seasonal scales. Temperature, vertical mixing, tidal flushing, climate, precipitation and nutrient loading can change the estuarine environment and subsequently alter microbial community structure, including Vibrio spp., affecting estuarine water quality and public health. To describe these dynamics, Vibrio spp. concentrations and a range of microbial, physical and chemical measures were monitored every 2 weeks and after storm events for 19 months in the Neuse River Estuary (NRE). Results showed clear seasonal and geographic trends in Vibrio spp. abundance. Multiple regression analysis revealed a strong relationship to temperature and salinity, with additional minor influences of chlorophyll a and dissolved organic carbon. Similar models based on easily measured environmental parameters should be pursued for individual Vibrio species in the NRE and other estuarine environments. Predictive models provide useful information for managers, researchers and modellers of estuarine ecosystems.