Cholera has reemerged as a global killer with the world witnessing an unprecedented rise in cholera infection and transmission since the 1990s. Cholera outbreaks across most affected areas show infection patterns with a single annual peak. However, cholera incidences in the Bengal Delta region, the native homeland of cholera, show bi-annual peaks. The mechanisms behind this unique seasonal dual peak phenomenon in cholera dynamics, especially the role of climatic and hydrologic variables, are not fully understood. Here, we show that low flow in the Brahmaputra and the Ganges during spring is associated with the first outbreaks of cholera in Bangladesh; elevated spring cholera outbreaks are seen in low discharge years. Peak streamflow of these rivers, on the other hand, create a different cholera transmission environment; peak flood volumes and extent of flood-affected areas during monsoon are responsible for autumn cholera outbreaks. Our results demonstrate how regional hydroclimatology may explain the seasonality and dual peaks of cholera incidence in the Bengal Delta region. A quantitative understanding of the relationships among the hydroclimatological drivers and seasonal cholera outbreaks will help early cholera detection and prevention efforts.