Background While some studies suggest that nutritional supplementation may reduce aggressive behavior in children, they have not examined whether its efficacy may be enhanced in conjunction with other treatment approaches. This study tests the hypothesis that a nutritional supplementation of omega‐3, multivitamins, and minerals over 3 months, combined with cognitive behavior therapy, will reduce childhood aggression. Methods In this randomized, single‐blind, stratified, factorial trial, a high‐risk community sample of 290 children aged 11–12 years were randomized into Nutrition only, cognitive behavioral therapy (CBT) only, Nutrition + CBT, and Control groups. The primary outcome measures of child‐ and parent‐reported aggressive and antisocial behavior were collected at 0 months (baseline), 3 months (end of treatment), 6 months (3 months posttreatment), and 12 months (9 months posttreatment). The trial (‘Healthy Brains & Behavior: Understanding and Treating Youth Aggression (HBB)’ was registered at ClinicalTrials.gov at https://clinicaltrials.gov/ct2/show/NCT00842439 Results For child self‐reports, children in the Nutrition only group showed reduced externalizing behavior compared to Controls at 3 months. At 6 months, the Nutrition + CBT group scored lower on externalizing behavior compared to both CBT only and Control groups. Findings were more in evidence for an Aggressive‐Reactive form of antisocial behavior than for a Callous‐Proactive form. Effect sizes were in the small‐to‐medium range (d = −.33 to −.37). Group differences were not sustained 9 months posttreatment, and no other effects were significant. Conclusions Findings provide some limited support for the efficacy of omega‐3, vitamin, and mineral supplementation in reducing aggressive behavior in children, and represent the first evaluation of nutritional supplements in conjunction with CBT.