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AbstractWomen in many sub-Saharan African countries are at elevated risk of depression during pregnancy. However, there are still gaps in the estimates of antenatal depression and associated risk factors in very low-resource settings such as Northern Ghana. This study describes the prevalence of depression among rural pregnant women, participating in a maternal and child health program, in Ghana, and examines associated risk factors for depression. Pregnant women who were registered for group-based maternal and child health community programs were recruited for study participation from 32 communities in two rural districts in Northern Ghana (n = 374). Baseline surveys were conducted and depression was assessed using the Patient Health Questionnaire (PHQ-9). Bivariate and multivariable analyses used a modified Poisson and generalized estimating equations (GEE) model. Of the women in our study population, 19.7% reported symptoms indicative of moderate to severe depression (PHQ-9 score ≥ 10), with 14.1% endorsing suicidal ideation in the last 2 weeks. Bivariate analyses revealed that lower hopefulness, moderate and severe hunger, experiences of emotional, physical, and/or sexual intimate partner violence (IPV), and insufficient social support from female relatives were associated with symptoms indicating moderate to severe depression. In the multivariable analyses, low hopefulness, household hunger, emotional IPV, physical and/or sexual IPV, and insufficient female relative support remained significantly associated with depression. Antenatal depression is associated with unmet basic needs and safety. Perinatal mental health programming must take an ecological perspective and address personal, familial, and community-level factors.