Prenatal stress alters fetal programming, potentially predisposing the ensuing offspring to long-term adverse health outcomes. To gain insight into environmental influences on fetal development, this QF2011 study evaluated the urinary metabolomes of 4-year-old children (n = 89) who were exposed to the 2011 Queensland flood in utero. Proton nuclear magnetic resonance spectroscopy was used to analyze urinary metabolic fingerprints based on maternal levels of objective hardship and subjective distress resulting from the natural disaster. In both males and females, differences were observed between high and low levels of maternal objective hardship and maternal subjective distress groups. Greater prenatal stress exposure was associated with alterations in metabolites associated with protein synthesis, energy metabolism, and carbohydrate metabolism. These alterations suggest profound changes in oxidative and antioxidative pathways that may indicate a higher risk for chronic non-communicable diseases such obesity, insulin resistance, and diabetes, as well as mental illnesses, including depression and schizophrenia. Thus, prenatal stress-associated metabolic biomarkers may provide early predictors of lifetime health trajectories, and potentially serve as prognostic markers for therapeutic strategies in mitigating adverse health outcomes.