Sheep and goat pox virus (SGPV) is a systemic contagious disease causing extreme illness and death in small ruminants.A cross-sectional study was conducted in West Gojjam and Awi zone of Amhara national regional state Northwest Ethiopia, from November 2018 to May 2019 with the objective of pox virus outbreak investigation and molecular detections in sheep and goats (shoats). The study included clinical examinations of lesions, laboratory analysis, and questionnaire survey. Study locations were selected randomly when an active outbreak was reported and observed.A total of 485 small ruminants (303 sheep and 182 goats) suspected of shoat pox were examined for the presence of specific skin lesions, 71 (14.64%) showed pox lesions, 35 (11.55%) sheep and 36 (19.78%) goats, and 24 (4.95%) had died. The study revealed highest morbidity rate in Jawie (31.25%) and Gunagua (14.89%) districts in goats and sheep, respectively. Lowest morbidity rate was recorded in Dega Damot district in sheep (6.45%) and goats (7.14%), respectively. The mortality rate was >1% in all districts except Dega Damot for both species. From a total of 38 tissue samples, 19 samples were selected based on the geographical distribution. All 19 samples (6 sheep and 13 goats) were found to be positive for goat pox virus based on polymerase chain reaction results. The significant risk factors were free animal movements, age, flock size and composition, body condition, vaccination status, and season. The study showed that in the absence of free movement of animals, the disease was less likely to occur (OR = 0.05, CI 95%; 0.02, 0.15).The disease was found in higher rate during the dry and short rainy season. Sheep were also found to be infected by goat pox virus. The study indicated that there was widespread sheep and goat pox in Northwest Ethiopia.