: Lipid metabolism plays an important role in maternal health and fetal development. There is a gap in the knowledge of how lipid metabolism changes during pregnancy for Black women who are at a higher risk of adverse outcomes. We hypothesized that the comprehensive lipidome profiles would show variation across pregnancy indicative of requirements during gestation and fetal development. : Black women were recruited at prenatal clinics. Plasma samples were collected at 8-18 weeks (T ), 22-29 weeks (T ), and 30-36 weeks (T ) of pregnancy. Samples from 64 women who had term births (≥37 weeks gestation) were subjected to "shotgun" Orbitrap mass spectrometry. Mixed-effects models were used to quantify systematic changes and dimensionality reduction models were used to visualize patterns and identify reliable lipid signatures. : Total lipids and major lipid classes showed significant increases with the progression of pregnancy. Phospholipids and glycerolipids exhibited a gradual increase from T to T to T , while sphingolipids and total sterol lipids displayed a more pronounced increase from T to T . Acylcarnitines, hydroxy acylcarnitines, and Lyso phospholipid levels significantly decreased from T to T . A deviation was that non-esterified fatty acids decreased from T to T and increased again from T to T , suggestive of a potential role for these lipids during the later stages of pregnancy. The fatty acids showing this trend included key fatty acids-non-esterified Linoleic acid, Arachidonic acid, Alpha-linolenic acid, Eicosapentaenoic acid, Docosapentaenoic acid, and Docosahexaenoic acid. : Mapping lipid patterns and identifying lipid signatures would help develop intervention strategies to reduce perinatal health disparities among pregnant Black women.