Prenatal exposure to per- and polyfluoroalkyl substances (PFAS), a ubiquitous class of chemicals, is associated with adverse outcomes such as pre-eclampsia, low infant birth weight, and later-life adiposity. The objectives of this study were to examine PFAS levels in the placenta and identify sociodemographic risk factors in a high-risk pregnancy cohort (n = 122) in Chapel Hill, North Carolina. Of concern, PFOS, PFHxS, PFHpS, and PFUnA were detected above the reporting limit in 99, 75, 55, and 49% of placentas, respectively. Maternal race/ethnicity was associated with significant differences in PFUnA levels. While the data from this high-risk cohort did not provide evidence for an association with hypertensive disorders of pregnancy, fetal growth, or gestational age, the prevalence of detectable PFAS in the placenta suggests a need to biomonitor for exposure to PFAS during pregnancy. Future research should investigate factors underlying the differences in PFAS levels in association with a mother's race/ethnicity, as well as potential effects on pregnancy and child health.