Gojjam is located in northwest Ethiopia, and it has been one of the densely populated areas of the country, except in the western parts of the province during the period understudy. In the past, people were severely affected by human epidemics. Of these epidemics, smallpox was one of the most contagious diseases which affected the people of Gojjam. It had killed, disfigured, blinded, and caused other physical damage which in turn had socio-economic implications. However, this historical reality had not been well studied except some paragraphs in the study of other historical themes of the region. Thus, the major objective of this thesis is to examine and reconstruct the history of smallpox epidemic in Gojjam between the 1950s and 1979. The study also looked at the socio-economic impacts of smallpox including the steps taken by the community, government, and international organizations to alleviate the disease. The sources used for the study are primary and secondary. This includes archives governmental reports, articles, journals, and other published and unpublished materials. Furthermore, I was able to collect relevant data from oral sources through interviews in different places of Gojjam. All data which obtained from informants cross-checked with archival as well as other sources to analyzed the authenticity and validity of them. This was made both thematically and chronologically. The findings of this study showed that a numbers of the people of Gojjam were affected by periodical smallpox outbreaks. The problem was aggravated by the inadequacy of medication and prevention methods as well as social factors. Although the communities and the government had attempted to eradicate this epidemic since 1950s, it was eradicated only after Gojjam became involved in the global smallpox eradication program with the great deed of international communities’ involvement. Finally, the paper attempts to explore the communities’ response, government, and international organization roles as well as identify the impact of smallpox in Gojjam