Rural American Indian (AI) middle school students with depressive symptoms who participated in a culturally modified version of the Adolescent Coping with Depression (CWD-A) course (n = 8) reported significant improvement in depressive symptoms at post-intervention and at 3-month follow-up. There was also a nonsignificant but clinically relevant decrease in participants' anxiety symptoms. Students reported satisfaction with the intervention, and it was potentially more cost-effective and less stigmatizing than the individualized treatment-as-usual interventions to which it was compared. These results suggest the CWD-A is a promising approach for reducing depressive and anxiety symptoms in rural AI students and should be further evaluated with a larger sample of students. (Contains 1 table.)