<p>Exposure to racial discrimination is a well-documented risk factor for adverse pregnancy outcomes. It is hypothesized that this association occurs through epigenetic changes. Researchers have identified associations between perceived discrimination and methylation of stress-response genes among racially and ethnically minoritized women. However, findings are limited by small sample sizes and inclusion of women who are several years postpartum. Little is known about the influence of discrimination on DNA methylation among Black women in pregnancy. Therefore, we conducted an epigenome-wide association study of 897 Black pregnant women who participated in the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-be (nuMoM2b) study to examine associations between experiences of racial discrimination and DNA methylation. Racial discrimination was measured using responses to the Experiences of Discrimination scale (range 0–9) completed in the second trimester of pregnancy. We dichotomized responses into low discrimination (0–2) and high discrimination (≥ 3) categories. Whole blood was collected in the first trimester of pregnancy and used for DNA extraction. We identified 130 CpG sites significantly associated with high levels of racial discrimination. There were 17 genes mapped to the 20 most significant CpG sites. Fourteen of those genes have disease-associated phenotypes including cancer (<i>LCMT2, LINC02753, RARA, HSP90AA1, SMTN, LPCAT1, SPAG4, DAPK1, ZNF500</i>), cardiomyopathy (<i>SMTN</i>), ovarian insufficiency (<i>DMRT3)</i>, neurodevelopmental disability (<i>MLPH</i>, CDC123, <i>OGFOD3</i>), and asthma (<i>STAT6</i>). We identified novel associations between racial discrimination and disease-related genes among Black nulliparous pregnant women. Future research should include structural racism measures and study epigenetic pathways between racism and adverse pregnancy and birth outcomes.</p>