BACKGROUND: Depression is the most common mental health outcome of exposure to war-related traumatic stressors. Due to inter-communal conflict, Dessie City residents have experienced prolonged armed conflict in 2021. This conflict leads to widespread violence, negative impact on mental health, and large-scale forced migration. However, the problem is not properly addressed in Ethiopia. Therefore, this study aimed to assess the prevalence and risk factors of depression in the war-affected area in Dessie City, Ethiopia. METHOD: A cross-sectional study design was conducted among 785 participants in 2022. The study subjects were selected using a multi-stage cluster sampling technique. The outcome measures used in the study were validated with the Patient Health Questionnaire (PHQ-9). Data was entered using Epi-data version 3.1 and SPSS version 25 was used to analyze data. Bivariate and multivariable logistic regressions were done to identify factors related to depression. In multivariable logistic regression variables with a p-value less than 0.05 were considered significant and, adjusted OR (AOR) with 95% CI was used to present the strength of the association. RESULT: The prevalence of depression among participants was found to be 24.5% (95% CI,21.7, 27.5). In multivariable analysis, post-traumatic stress disorder (AOR = 2.79, 95% CI 1.76-4.43), middle-perceived life threats (AOR = 8.25, 95% CI 2.47-17.49), low social support (AOR = 1.90, 95% CI 1.23-2.96) were variables significantly associated with depression. CONCLUSION: This study found a high prevalence of depression among Dessie City residents. post-traumatic stress disorder, middle-perceived life threats, and low social support were associated with depression. Interventional strategies should be implemented to promote healing, resilience, and the overall well-being of individuals and communities. However, the findings underscore the need to address the current lack of mental health care resources in post-conflict populations.