Family systems therapy has shown to be a powerful adjunct to substance use treatment for couples and for adolescent substance users (Rowe, 2012). However, studies including children (8−16 years of age) in the treatment of their substance using mothers have been overlooked and are essentially nonexistent. Addressing the quality of the mother–child relationship and communication through family systems therapy may prove to be a potent intervention focus for improving mothers’ substance use outcomes and parent–child interaction. As such, the current study recruited 183 mothers who sought outpatient treatment through a local substance use treatment facility and randomly assigned them to also receive family systems therapy or Women’s Health Education. Self-report and observational data were collected, and assessment interviews were completed at baseline and 3, 6, 12, and 18 months postbaseline. Findings showed that women assigned to family systems therapy showed a quicker decline in alcohol, marijuana, and cocaine use, supporting the efficacy of family therapy as an important addition to mother’s substance use treatment plans. Data also revealed an association between change in observed autonomy-relatedness and substance use, though mediation was not found. To our knowledge this is the first effort to successfully document a family systems therapy for substance using mothers with minor children in their care.