This paper explores how the medicinal plant knowledge of the Waorani indigenous society in Ecuador varies in accordance with both socio-economic and demographic factors. Medicinal plant knowledge was compared at both individual and community levels. Fifty-nine semi-structured interviews (men n = 30, women n = 29) were performed with people between fifteen and seventy years old in five Waorani communities located within the Yasuní Biosphere Reserve. Results show a positive correlation between an individual’s medicinal plant knowledge and age, a negative correlation between medicinal plant knowledge and the years of schooling, and differences among isolated and easily accessible communities. Reasons behind these findings are seen in the rapid socio-cultural changes of the Waorani society due to globalization processes. Increased accessibility to health centers, improved transportation infrastructure and changes in how knowledge is transmitted to young people all result in a loss of ethnobotanical knowledge. Policymakers need to take action in order to ensure the maintenance of ethnoecological knowledge among the Waorani.