The hydrological conditions of the Lower Mekong Basin support a multitude of ecosystem services. Processes that influence water flow in the Mekong River will thus have implications for the tens of millions of people whose livelihoods depend on these services. This study presents an assessment of livelihood susceptibility to hydrological change in the Lower Mekong Basin. Using an index‐based approach, susceptibility scores were calculated for 2,703 households. Using those scores, we compared average household susceptibility across the basin, among countries and among eco‐zones. Due to their greater livelihood dependency on water‐related activities, mean household susceptibility was higher in Vietnam than in Cambodia, Laos, or Thailand. Households in Northern Laos also had high susceptibility, which was attributed to their low adaptive capacity. The findings suggest that policies aimed at reducing vulnerability to hydrological change in the Lower Mekong Basin should account for geographic context. Further, they highlight how policies may be able to strategically target the most susceptible households, but that poorly designed policies have the potential to exacerbate vulnerability. In the face of high uncertainty surrounding hydrological change in the Lower Mekong Basin, our assessment of susceptibility should help inform precautionary water management policies and provide baseline information needed for more comprehensive vulnerability assessments.