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Factors that affect children's school readiness potential are evident from birth. Structural equation modeling was used to test the hypotheses that certain factors related to family risk conditions, the quality of prenatal care, maternal health during pregnancy, and the health status of the child at birth mediate children's readiness for school. Data from the Early Childhood Longitudinal Study – Birth Cohort (ECLS-B) was used to test the hypotheses. 10,688 children were included in the sample and represented diverse socioeconomic and racial/ethnic backgrounds. The hypothesized model suggested that there were both direct and indirect influences on children's school readiness performance. Potential risk factors were identified and implications for ameliorating negative influences are identified.