Despite considerable progress in characterizing the early signs of autism spectrum disorder (ASD), more remains to be learned about how symptoms emerge in the first year of life. Parents with a new baby who already had at least one biological child diagnosed with ASD (high-risk) or no family history of ASD (low-risk) completed two measures when their baby was 9 months of age, the Autism Parent Screen for Infants (APSI) questionnaire and the interview-based Parent Concerns Form. Children underwent a blinded independent diagnostic assessment for ASD at age 3 years. Total scores on the APSI and the Parent Concerns Form were both able to independently differentiate high-risk children who were later diagnosed with ASD from other high-risk and low-risk children who were not. Using logistic regression, we found that the total score on the APSI predicted ASD outcomes at age 3 with 70% accuracy, but the Parent Concerns Form did not contribute any unique variance when the APSI was already in the model. The results suggest that the APSI identifies early features predictive of ASD in high-risk infants and can be used to flag them for targeted follow-up and screening.