Background Both antenatal and postpartum depression have adverse, lasting effects on maternal and child well‐being. Socioeconomically disadvantaged women are at increased risk for perinatal depression and have experienced difficulty accessing evidence‐based depression care. The authors evaluated whether “MOMCare,”a culturally relevant, collaborative care intervention, providing a choice of brief interpersonal psychotherapy and/or antidepressants, is associated with improved quality of care and depressive outcomes compared to intensive public health Maternity Support Services (MSS‐Plus). Methods A randomized multisite controlled trial with blinded outcome assessment was conducted in the Seattle‐King County Public Health System. From January 2010 to July 2012, pregnant women were recruited who met criteria for probable major depression and/or dysthymia, English‐speaking, had telephone access, and ≥18 years old. The primary outcome was depression severity at 3‐, 6‐, 12‐, 18‐month postbaseline assessments; secondary outcomes included functional improvement, PTSD severity, depression response and remission, and quality of depression care. Results All participants were on Medicaid and 27 years old on average; 58% were non‐White; 71% were unmarried; and 65% had probable PTSD. From before birth to 18 months postbaseline, MOMCare (n = 83) compared to MSS‐Plus participants (n = 85) attained significantly lower levels of depression severity (Wald's χ2 = 6.09, df = 1, P = .01) and PTSD severity (Wald's χ2 = 4.61, df = 1, P = .04), higher rates of depression remission (Wald's χ2 = 3.67, df = 1, P = .05), and had a greater likelihood of receiving ≥4 mental health visits (Wald's χ2 = 58.23, df = 1, P < .0001) and of adhering to antidepressants in the prior month (Wald's χ2 = 10.00, df = 1, P < .01). Conclusion Compared to MSS‐Plus, MOMCare showed significant improvement in quality of care, depression severity, and remission rates from before birth to 18 months postbaseline for socioeconomically disadvantaged women. Findings suggest that evidence‐based perinatal depression care can be integrated into the services of a county public health system in the United States. Clinical Trial Registration: ClinicalTrials.govNCT01045655.