American Indian (AI) children have the highest rates of obesity among ethnic groups in the United States, and rates continue to increase. This study was designed to examine the effects of prenatal and early postnatal factors on AI children's body mass index (BMI) trajectories, adiposity, and cardiovascular risk markers during early childhood. We screened 471 AI children (ages 5-8) from three Wisconsin tribes. Screenings included anthropometric and body fat measures and non-fasting lipid and glucose via fingerstick blood samples. Tribal records from Women Infants and Children (WIC) programs and clinic charts provided data on children's BMI trajectories, maternal prenatal factors, and the early postnatal feeding environment. Forty-seven percent of children were overweight or obese. Analysis of growth trajectories showed that children's BMI category was largely determined within the 1 year of life. Significant predictors of children's BMI category at age 1 included macrosomia (OR 4.38), excess gestational weight gain (OR 1.64) and early termination of breastfeeding (OR 1.66). Children who were overweight/obese at age 1 had greater odds of being overweight (OR 3.42) or obese (OR 3.36), and having unhealthy levels of body fat (OR 2.95) and LDL cholesterol (OR 1.64) at ages 5-8. Children's BMI category is determined in the early post-natal environment, within the 1 year of life, by factors including excess gestational weight gain and early termination of breastfeeding. In turn, children's BMI category at age 1 predicts the emergence of cardiovascular risk markers in early childhood.