Although heterogeneity in the timing and persistence of maternal depressive symptomatology has implications for screening and treatment as well as associated maternal and child health outcomes, little is known about this variability. A prospective observational study of 1,735 low-income, multiethnic, inner-city women recruited in pregnancy from 2000 to 2002 and followed prospectively until 2004 (1 prenatal and 3 postpartum interviews) was used to determine whether distinct trajectories of depressive symptomatology can be defined from pregnancy through 2 years postpartum. Analysis was carried out through general growth mixture modeling. A model with 5 trajectory classes characterized the heterogeneity seen in the timing and magnitude of depressive symptoms among the study participants from Philadelphia, Pennsylvania. These classes included the following: 1) always or chronic depressive symptomatology (7%); 2) antepartum only (6%); 3) postpartum, which resolves after the first year postpartum (9%); 4) late, present at 25 months postpartum (7%); and 5) never having depressive symptomatology (71%). Women in these trajectory classes differed in demographic (nativity, education, race, parity) health, health behavior, and psychosocial characteristics (ambivalence about pregnancy and high objective stress). This heterogeneity should be considered in maternal depression programs. Additional research is needed to determine the association of these trajectory classes with maternal and child health outcomes.