Climate change is one of the major contributing factors to degradation of ecological services, and these in turn are harming many people and causing poverty mainly in rural areas. The information available and the gain of knowledge on how climate change is affecting livelihood resources in the Bolivian Andes are very limited. This research aims to advance in the understanding of adaptive capacity to social and climate change in rural communities whose livelihoods are dependent upon agriculture and local resources. The proposed framework of this research focuses on the vulnerability assessment of the socio-ecological system, which targets on the identification of adaptation strategies in the context of their contribution to the overall adaptive capacity of the system. Following an exploratory design, two representative communities from different agro-ecological regions are selected as case studies: Santiago de Okola (Municipality of Puerto Carabuco, highlands) and Sita-Chorocana (Municipality of Inquisivy, inter-Andean valley). The research is conducted using a participatory rural appraisal approach and combines indicators encompassing natural, physical, human, financial, and socio-cultural variables. Data collection is based on community discussion (n=6), key informant interviews (n=31), household interviews (n=125), and local observations. Data analysis is conducted for quantitative and qualitative information. The results are presented in four main sections: 1) Integral diagnosis of the current situation in each case study considering general characteristics of the population, agriculture activities and forest resources; followed by a complete description of impacts and strategies to cope with extreme weather events and socio-economic conflicts at household level. 2) The assessment of strategies based on cultural knowledge describes the existing traditional ecological knowledge and local customs. Moreover, a mathematical model has been developed to evaluate the current knowledge needed to cope with and adapt to climate change. The outcomes point out that for the highlands the diversification of knowledge, and for the inter-Andean valley the social—pooling are strategies that contributed the most to secure crop production under extreme weather event scenario. 3) The assessment of socio-economic strategies identifies households under the category of poor as the most vulnerable group to climate change; this group is dominated by old women living alone in the communities and in charge of the farm. Based on the redundancy analysis poverty indicators have been identified: In the highlands, off-farm activities represent a potential strategy whenever the crop production is reduced or limited; these activities are related to the labor availability in the household, health conditions and level of education. In the inter-Andean valley, out-farm and eucalyptus plantations represent a potential strategy to secure crop production when households have access to land and markets and they participate in social networks. 4) The assessment of social networks identifies the relationship between the households, stakeholders, and the municipality to cope with socio-economic conflicts and the impacts of extreme weather events. Independently of each case study, the outcomes point out the existing social networks under socio-economic scenario contributed to the implementation of a wide number of coping strategies to secure in the long-term the well-being of the household including economic development, food production, education, social organization, infrastructure, and health. The existing social networks under the extreme weather events scenarios contributed mainly to secure food production of the households by providing immediate access to labor. This research presents evidence on how social and climate changes are the major contributing factors to increasing vulnerability of the socio-ecological system. It is the first explorative research in which cultural knowledge, socio-economic and social networks strategies are integrated to understand the adaptive capacity of rural communities in the selected case studies. The livelihood adaptation strategies identified independently of each of the two case study eco-regions showed particular characteristics related to the lifestyle, the knowledge and the socio-economic resources available in the communities; and highlights the potentialities and limitations of the households to reduce their vulnerability. Finally, the proposed model towards adaptive capacity is a tool that can be used to guide new policies and programs that target poverty reduction and minimize the adverse impacts of climate change.