Depression in childhood is a significant mental health concern, impacting cognitive, affective, social, behavioral, and physical domains. Children who experience depressive symptoms are at an increased risk for physical and mental health, social, and behavioral problems throughout adulthood. Children who are marginalized due to their socioeconomic status, racial and ethnic identities are at an increased risk to experience depression and limited access to mental health care. Further, previous research has demonstrated limited efficacy of depression treatments for young children. This study is an examination of the efficacy of child-centered play therapy [CCPT], a culturally and developmentally responsive treatment, on depression among young children. Participants were 71 children from five Title 1 elementary schools in the southwestern U.S. referred by school personnel for depressive symptoms (49 males, 22 females; ages 5–9, mean age M = 6.21). The sample consisted of 14 (19.7%) African American, three (4.2%) Asian American, 15 (21.1%) biracial, 19 (26.8%) Caucasian, and 20 (28.2%) Latino children. Participants were randomly assigned to eight weeks of twice-weekly CCPT experimental groups (n = 34) or a waitlist control group (n = 37). Results of doubly multivariate repeated-measures MANOVA revealed statistically significant improvement in depressive symptoms for children who participated in CCPT on the Mood and Feelings Questionnaire Parent and Direct Observation Form [DOF] Sluggish Cognitive Tempo Scale. Repeated measures ANOVA on DOF Total Problems indicated that children in CCPT statistically significantly decreased their demonstration of overall problem behaviors as rated by blind observers. Results of this study support the effectiveness of CCPT with young children of diverse ethnocultural and socioeconomic background.