Background: The worldwide prevalence of scabies has been estimated to be about 200 million cases per year and is common in underdeveloped world in general and sub-Saharan African countries in particular. Ethiopia remains one of the high burden countries in scabies infestation; hence age specific investigation of scabies has been done in some parts of the country, however determinants of scabies among general population level are not well identified. Method: A community based unmatched case-control study design among 351 participants (117 cases and 234 controls) was conducted in Ziquala district of northeast Ethiopia from March to April 2021. The study participants were selected using multistage cluster sampling technique. Data were collected using structured interviewer administered questionnaire. Data were entered, coded and cleaned using Epidata version 3.1 software packages, and analyzed by using SPSS version 23 statistical software package. All variables with p-value < 0.25 in bivariable logistic regression analysis were selected for multivariable logistic regression analysis and statistical significance was declared at p =< 0.05. The Hosmer-Lemeshow test was utilized to check whether the model is fitted or not. Result: Family history of itching (AOR=6.6, 95% CI: (2.78-15.62), sharing of cloths with scabies affected person (AOR=3.67, 95% CI: (1.03-13.16), absence of hand washing facility nearby latrine, (AOR=4.24, 95% CI: (1.88-9.53), poor knowledge about scabies (AOR=3.98, 95% CI:(1.81-8.78), family size ≥ 5 in the household (AOR=2.24, 95% CI: (1.13-4.75), and not visiting health facility in the last six months (AOR=4.24, 95% CI: (1.79-10.9, were found to be determinants of scabies infestation. Conclusion: In this study, family history of itching in the household, family size greater than or equal to five, sharing of clothes with scabies infected person, not visiting of health facility in the last 6 month and absence of hand washing facility nearby latrine were positively associated with scabies infestation. Awareness creation should be done to increase health seeking behavior of the community towards health facilities and exchanging of cloths should be avoided between family members as well as with others persons. Key words: Determinants of scabies, Scabies, Ziquala district, Ethiopia