A study on ectoparasites of small ruminants in three selected agro-ecological sites of Tigray Region, Ethiopia disclosed an overall prevalence of 55.5% and 58% in each examined 750 sheep and goats, respectively. In the sheep population, Melophagus ovinus (19.1%), tick infestations (16%), Damalinia ovis (15.3%), Linognathus africanus (11.5%), and Ctenocephalides felis (9%) were the major ectoparasites. The major ectoparasites identified in goats were tick infestations (29.7%), L. africanus (27.9%), Sarcoptes scabiei var. caprae (12.5%), C. felis (11.1%), and Demodex caprae (6.8%). In sheep, there was a statistically significant difference (P < 0.001) in the prevalence of Damalinia ovis, M. ovinus, L. africanus, and ticks between midland and highland. In goats, the risk of Sarcoptes scabiei var. caprae infestation in midland (odds ratio (OR) = 17.2, P < 0.001) and lowland (OR = 5.2, P < 0.001) was 17.2 times and 5.2 times, respectively, higher than the highland. Favorable climatic conditions, backward level of management, poor level of consciousness and awareness of farmers, and weak animal health extension services are believed to have contributed for widespread distribution and occurrences of ectoparasites. The growing threat of ectoparasites to small ruminant production and the tanning industry needs well-coordinated and urgent control intervention.