Background Childhood trauma increases the risks of both depression and dysfunctional emotion regulation, which is a factor that has been strongly linked to depression. Because of these demonstrated relationships, it can be hypothesized that dysfunctional emotion regulation is a mediator of the association between childhood trauma and depression. Methods To test this hypothesis, we assessed the indirect effect of emotion regulation (Emotion Regulation Skills Questionnaire) on the relationship between childhood trauma (Childhood Trauma Questionnaire) and depression severity (24-item Hamilton Rating Scale for Depression) as well as depression lifetime persistency (i.e., lifetime percentage spent in major depressive episodes; assessed via SCID and Life Chart Interviews) in 269 patients with major depressive disorder (MDD). Results Bootstrapping-enhanced mediation analyses indicated that deficits in general emotion regulation mediated the association of childhood trauma to both depression severity and depression lifetime persistency. Further exploratory analyses indicated that specific emotion regulation skills (such as the ability to mindfully observe, accept, and tolerate undesired emotions or the willingness to voluntarily confront situations that prompt negative emotions in order to attain personally relevant goals) significantly mediated the association between childhood trauma and depression severity. Willingness to confront was a mediator for both depression outcomes (depression severity and lifetime persistency). Limitations The employed mediation analyses are cross-sectional in nature, which limits any firm conclusions regarding causality. Conclusions The findings support the assumption that a sophisticated emotion regulation may help prevent the onset or unfavorable course of depression in individuals who have experienced childhood trauma.