Background Depressive disorders place an enormous burden on society and ranked fourth in the global disease burden accounting for 4.4% of the total disability-adjusted life years and 11.9% of total years lived with disability. Depression is associated with high level of morbidity and it is the most common contributor to suicide. Refugees have higher rates of mental disorders, in particular depression than those usually found in the non-war affected general population. There is a dearth of evidence in Ethiopia regarding the mental health of refugees. Objective This study aimed to assess the prevalence of depression and associated factors among Eritrean refugees in Tigray North Ethiopia. Methods A cross-sectional study was conducted at Maiayni refugee camp. A total of 800 participants were interviewed using systematic random sampling method. Pretested, structured and interviewer administered questionnaire that included socio demographic, clinical, behavioral, Harvard trauma questionnaire, and the patient health questionnaire (PHQ-9) was used. Descriptive statistics and binary logistic regression analyses were carried out. Results With 786 (98.3%) of response rate, the prevalence of depression was found to be 37.8%, 95% confidence interval (34.2, 41.2). The odds of depression was higher in females [(AOR=8.92 95% CI (5.21, 15.25)], older age [(AOR=2.72 95% CI (1.03–7.16)], those who never attended school [(AOR=3.09 95% CI (1.16–8.24)], among the unemployed [(AOR=2.36 95% CI (1.16–4.83)], those with poor social support [(AOR=8.67 95% CI (4.24–17.77)], past psychiatric history [(AOR=4.76 95% CI (1.94–11.67)], family history of a psychiatric disorder [(AOR=3.96 95% CI (1.93–8.13)], those who were using substances [(AOR=4.08 95% CI (2.51–6.65)], and among those who stayed for longer than a year at the camp [(AOR=4.18 95% CI (2.47–7.08))]. Conclusion The study revealed that depression is a major mental health and public health problem among Eritrean refugees in Ethiopia. Several socio-demographic, psychosocial, behavioral and clinical factors were significant predictors of depression among the study participants. Mental health service provision for the refugees needs to be part of the support.