At the U.S.—Mexico border, immigration policies have been documented to exacerbate health inequities among immigrant communities. We examined the prevalence of perinatal depressive symptomatology among Mexican-origin mothers living on the U.S.—Mexico border. Data for 1,629 pre- and postnatal women were drawn from a Community Health Worker Home Visiting Program from 2008 to 2016. Participants were screened for perinatal depressive symptomatology using the Edinburgh Postnatal Depression Scale (EPDS). Prevalence and associated 95% confidence intervals for prenatal and postnatal depression scores were estimated among women with prenatal depression scores only, postnatal depression scores only, and among women with both prenatal and postnatal scores by year and by participant characteristics. Participants were predominantly Mexican, Spanish-speaking, unmarried, with less than high school education, and with an annual income of less than $15,000. Prenatal and postnatal EPDS scores indicating low risk for depression (i.e., 0—5) ranged from 59.4% to 64.8% and 62.2% to 71.9%, respectively. Moderate risk prenatal and postnatal EPDS scores (i.e., 6—12) ranged from 28.6% to 32.1% and 22.8% to 25.6%, respectively. High-risk prenatal and postnatal EPDS scores (i.e., ≥13) ranged from 6.6% to 8.5% and 5.3% to 12.3%, respectively. In the context of a proliferation of anti-immigrant policies that jeopardize social determinants of maternal well-being, we observed a sustained upward trend in mean EPDS scores. U.S.—Mexico border women may be at particular risk for discrimination, stress, and victimization because of U.S. immigration and border security policies. This brief report generates a baseline prevalence of perinatal depressive symptomatology among women of Mexican origin and offers public health research explanations for maternal mental well-being at the U.S.—Mexico border. (PsycINFO Database Record (c) 2019 APA, all rights reserved)