Background: Mental health is the greatest challenges for the current and future generations. Worldwide, out of the 66 million people suffering from depression; majority (85%) were from low and middle income countries. The prevalence was more common among the prisons population than the community. However, a worldwide consideration given to the problems is very low, particularly for prisoners. Methods: To assess level of depression and associated factors among prisoners in prisons of Northwest Amhara Regional State, Ethiopia, Institutional based cross sectional study was employed on 727 prisoners selected by multistage random sampling from three prisons of northwest Amhara. Patient Health Questionnaire (PHQ-9) was used to assess an individuals' depression level. The reliability of the tool was checked by Cronbach's Alpha (yielding value of 0.841). Multivariable logistic regression was done to identify factors associated with depression after Hosmer and leme show goodness of fit test was used for model fitness. Results: Of the total prisoners participated (649), 284 (43.8%; 95% CI: 39.90, 47.67%) had symptoms of depression. Detainees' satisfaction level about life before imprisonment, belief about their life after imprisonment, plan to commit suicide, social support and types of prisons were significantly associated with depression. Conclusions: Depression level among detainees was found to be high. Thus, providing training to scale up satisfaction of prisoners, on how to cope up with environment just before imprisonment and release, and treating prisoners will improve the problem.