SummaryBackgroundChildhood obesity remains a public health crisis and identification of unique prenatal and early infancy predictors of obesity risk are critically needed.ObjectivesWe test a comprehensive biopsychosocial model of the predictors of rapid weight gain (RWG) in the first 6 months of life.MethodsTwo hundred and ninety nine pregnant women and their infants participated. Maternal prenatal psychobiological risk (PPBR) was assessed during the third trimester via maternal anthropometrics, serum biomarkers (insulin, leptin, adiponectin), and maternal report of pregnancy complications, substance use, mental health and stress. Infant stress reactivity was measured at 2 months (cortisol output, resting RSA, observed irritability, negative emotionality). At 2 and 6 months, maternal self‐report of obesogenic feeding practices and observed maternal sensitivity during three tasks were collected. RWG was classified based on change in weight‐for‐age z scores from birth to 6 months (>0.67 SD).ResultsObesogenic feeding practices predicted greater likelihood of RWG, β = 0.30, p = .0.01, independent of other predictors and covariates. Obesogenic feeding practices was the only proposed intervening mechanism that produced a significant indirect effect of PPBR on RWG, b = 0.05, S.E. = 0.04, 95% CI [0.002, 0.15], β = 0.06.ConclusionIdentifying proclivity towards obesogenic feeding practices and providing support to reduce these behaviours may enhance childhood obesity prevention efforts.