Vulnerability, understood as the propensity to be adversely affected, has attained importance in the context of climate change by helping to understand what makes populations and territories predisposed to its impacts. Conditions of vulnerability may vary depending on the characteristics of each territory studied—social, environmental, infrastructural, public policies, among others. Thus, the present study aimed to evaluate what makes the municipalities of the state of Amazonas, Brazil, vulnerable to climate change in the context of the largest tropical forest in the world, and which regions of the State are the most susceptible. A Municipal Vulnerability Index was developed, which was used to associate current socio-environmental characteristics of municipalities with climate change scenarios in order to identify those that may be most affected by climate change. The results showed that poor adaptive capacity and poverty had the most influence on current vulnerability of the municipalities of Amazonas with the most vulnerable areas being the southern, northern, and eastern regions of the state. When current vulnerability was related to future climate change projections, the most vulnerable areas were the northern, northeastern, extreme southern, and southwestern regions. From a socio-environmental and climatic point of view, these regions should be a priority for public policy efforts to reduce their vulnerability and prepare them to cope with the adverse aspects of climate change.