V. cholerae is mainly transmitted by the ingestion of drinking water or food contaminated with faeces or vomit. Given the fact that Vibrio cholera reacts very sensitively to gastric acid, the infection dose is relatively high and vehicle-dependent: 103 -106 (water) or 102 -104 (food). The dose required for infection is proportionately smaller for humans who produce less gastric acid (e.g. because of taking proton pump inhibitors).

In most cases, the agents are excreted for a few more days after the symptoms have ceased. In asymptomatic cases, the pathogens can be detected for 14 days. There have only been a few cases in which the pathogen has been excreted for several months. Direct transmission from human-to-human is rare.

Ecological niches also serve as reservoirs for V. cholerae and other species of Vibrio, in addition to the human body. Given the appropriate temperature, electrolyte and nutrient levels, Vibrio bacteria can survive in water for years. Not only can drinking contaminated water play a role in transmission, but direct contact with wounds can lead to infections, too.