Background Depression is a common mental disorder among prisoners characterized by a mood change involving a feeling of sadness, lack of interest, or hopelessness that lasts for weeks, months, or even longer. Besides imprisonment, depression is the primary factor leading to suicidal attempts. However, little is known about the depressive status of prisoners in Ethiopia. Therefore, this study aimed at assessing the magnitude and associated factors of depressive symptoms among prisoners of Debre Berhan prison. Methods We conducted an institution-based cross-sectional study. We collected data from 336 randomly selected prisoners using interviewer-administered Patient Health Questionnaire-9 (PHQ-9). We collected the data from May 3 to 28, 2015, and performed binary logistic regression to identify independent predictors of depressive disorder. Result Out of the total of 336 prisoners, 98% (n = 330) were males. Using PHQ-9 at the cutoff point of �5, we found the prevalence of depression to be 44% (n = 148). Being widowed (AOR = 6.30; CI: 1.09-36.67), having a college or university level educational status (AOR = 5.34; CI:1.59-17.94), having a history of suicide attempt (AOR = 2.76 CI: 1.04-7.31), having faced severe stressful life events (AOR = 2.57; CI: 1.41-4.67), being sentenced for 5 to 10 years (AOR = 2.51; CI:1.32-4.79), and having a history of chronic medical illness (AOR = 3.32 CI: 1.26-8.75) were found to be independently associated with depressive symptoms.