Study was conducted in two sub-districts in northwestern Ethiopia to compile and analyse knowledge on the use of medicinal plants for treatment or prevention of human ailments by three socio-cultural groups, namely the Amharas, Shinashas and Agew-Awis. Data were mainly collected through individual interviews conducted with selected knowledgeable farmers and professional healers of the three socio-cultural groups. A total of 76 medicinal plants belonging to 48 families were documented, of which 50 species were reported by the Amharas, 25 by the Shinashas and 20 by the Agew-Awis. Large proportions of medicinal plants were found to have been used for the treatments of gastro-intestinal complaints (26%), skin diseases (24%) and malaria (22%). Relatively, higher numbers of informants agreed on the use of Croton macrostachyus against malaria (21%), Cynoglossum coeruleum against ‘mich’, illness mainly characterized by fever, headache and sweating (18%) and Zehneria scabra against malaria (13%). The species Croton Macrostachyus, Calpurnia aurea, Clematis hirsuta and Plumbago zeylanica were found to have the highest diversity of medicinal applications. We recommend that priority for further investigation should be given to medicinal plants with higher informant consensuses, as this could indicate their better efficacy. Measures are needed to conserve plants that are reported as scarce in the study area but still are only harvested from the wild.