Objective: Youths with disruptive behavior disorders (DBDs) and a history of trauma exposure often exhibit deficits in neural mechanisms related to reward anticipation and assessment. This preliminary investigation examines the potential of a serotonergic agent (fluoxetine) to modulate neural activity in reward-related pathways for this population. Methods: Three participant groups were: (i) youth with DBDs and trauma exposure who received fluoxetine treatment for 8 weeks (n = 12); (ii) a matched group of youth with DBDs and trauma exposure who received routine regular followup in an outpatient clinic (n = 9); and (iii) typically developing youth (n = 19). All participants completed a passive avoidance fMRI task twice, 8 weeks apart (pre-treatment and post treatment for youth with DBDs). Results: Youth with DBDs and trauma exposure who received fluoxetine treatment compared to the other two groups showed: (i) significant improvement in externalizing, oppositional defiant disorder, irritability, anxiety-depression, and trauma-related symptoms; (ii) significantly increased recruitment of regions implicated in reward expectation (e.g., ventral tegmental area, nucleus accumbens), monitoring prediction error (e.g., dorsolateral prefrontal cortex, posterior parietal cortex), and inhibitory control (e.g., anterior insula, pre-supplementary motor area, anterior prefrontal cortex. Conclusion We provide preliminary data suggesting that a serotonergic medication can correct reward processing and provide symptom improvement in youth with DBDs and a history of trauma exposure. Given the small sample size, more rigorous studies with larger sample size are needed to confirm these results. The findings of this study could aid future clinical research and treatment for this challenging population.