--- - |2 Children of substance abusing parents are at heightened risk to develop problem behaviors, yet little is known about the co‐occurring patterns of internalizing and externalizing behaviors among this population. With 183 children (M age = 11.54 years, SD = 2.55, range 8–16) whose mothers were diagnosed with a substance use disorder, the current study identified subgroups/classes of children that were clinically distinct in their co‐occurring patterns of internalizing and externalizing behaviors, and examined how children in different clinical subgroups responded to a family systems intervention. Latent class analyses identified four classes of internalizing and externalizing behaviors: internalizing only, externalizing only, comorbid, and normative. Latent transition analyses showed that participation in family systems therapy resulted in an increased likelihood of transitioning from the externalizing class at baseline to the normative class at 18 months post‐baseline, and from the comorbid class at baseline to the internalizing class at 18 months post‐baseline as well. The findings support the effectiveness of family systems therapy in interrupting the stability of children's problem behaviors and improving children's behavioral outcomes. - Journal of Marital and Family Therapy, Volume 44, Issue 4, Page 687-701, October 2018.