A cross sectional study was conducted from November 2018 to May 2019 in selected districts of West and Awi zones Northwest, Ethiopia with the aim of outbreak investigation and molecular detection of pox virus circulating in sheep and goats. The study was engaged different outbreak investigation approaches including clinical examinations and lesions, laboratory analysis and questionnaire survey. The districts and rural kebeles were selected randomly when an active outbreak of the diseases were reported and observed. From a total of 485 small ruminants (303 sheep and 182 goats) clinically examined for presence of specific skin lesions suspected of sheep and goat pox, 71 (14.64%) showed pox lesions of which 35 (11.55%) sheep and 36 (19.78%) goats manifested clinical signs and lesions suggestive for the diseases and 24 (4.95%) were dead during the outbreaks of sheep and goat pox. The study revealed that the highest morbidity of the disease was found in Jawie (31.25%) and Gunagua (14.89%) districts in goats and sheep respectively. The lowest was recorded in Dega Damot district both in sheep and goats which was 6.45% and 7.14% in sheep and goats respectively. However, the mortality rate was >1% in all districts except Dega Damot which was not found in both species. From a total of 38 skins tissue samples randomly collected from 71 sheep and goats showing typical pox lesions 19 samples were selected based on geographical distribution for molecular detection of the virus. All 19 samples (6 sheep and 13 goats) were found to be positive with goat pox virus. Even though the previous information suggested that Capripoxvirus is strictly host specific, however, sheep were found infected by goat pox virus in the current study suggesting that classification of pox virus based on infected host in small ruminant needs re-considerations. The significant potential risk factors were free animal movements, age of sheep and goats, flock size and composition, body conditions, vaccinations status and season of the year. The study showed that in the absence free movement of animals the diseases was less likely to occur with, (OR=0.05, CI 95%; 0.02, 0.15) and in the absence of vaccination small ruminants were more affected with, (OR=0.01, CI 95%; 0.00, 0.05). Keywords: Amhara, Epidemiology, Ethiopia, Outbreak, Pox virus, Sheep and Goat