Members of the genusVibrioare ecologically significant bacteria native to aquatic ecosystems globally, and a few can cause diseases in humans. Vibrio-related illnesses have increased in recent years, primarily attributed to changing environmental conditions. Therefore, understanding the role of environmental factors in the occurrence and growth of pathogenic strains is crucial for public health. Water, oyster, and sediment samples were collected between 2009 and 2012 from Chester River and Tangier Sound sites in Chesapeake Bay, Maryland, USA, to investigate the relationship between water temperature, salinity, and chlorophyll with the incidence and distribution ofVibrio parahaemolyticus(VP) andVibrio vulnificus(VV). Odds ratio analysis was used to determine association between the likelihood of VP and VV presence and these environmental variables. Results suggested that water temperature threshold of 20°C or higher was associated with an increased risk, favoring the incidence ofVibrio spp. A significant difference in salinity was observed between the two sampling sites, with distinct ranges showing high odds ratio forVibrioincidence, especially in water and sediment, emphasizing the impact of salinity on VP and VV incidence and distribution. Notably, salinity between 9-20 PPT consistently favored theVibrioincidence across all samples. Relationship between chlorophyll concentrations and VP and VV incidence varied depending on sample type. However, chlorophyll range of 0-10 µg/L was identified as critical in oyster samples for both vibrios. Analysis of odds ratios for water samples demonstrated consistent outcomes across all environmental parameters, indicating water samples offer a more reliable indicator ofVibrio spp.incidence.ImportanceUnderstanding the role of environmental parameters in the occurrence ofVibriospecies posing significant public health risks and economic burdens such asVibrio parahaemolyticusandVibrio vulnificusare of paramount importance. These aquatic bacteria are responsible for various human diseases, including gastroenteritis and wound infections, which can be severe and sometimes fatal. Recent observations suggest that certain environmental conditions may favor the growth ofVibrio, leading to more severe disease outcomes. By investigating the environmental factors that influence the occurrence ofVibrio parahaemolyticusandVibrio vulnificus, the need to gain insights into the favorable ranges of environmental variables is apparent. The significance of this research is in identifying the favorable ranges of environmental and ecological factors, which holds the potential to provide an aid in the intervention and mitigation strategies through the development of predictive models, ultimately enhancing our ability to manage and control diseases caused by these pathogens.