Objective. To measure upper-extremity and gross motor skill development in infants with and without risk factors for autism spectrum disorder (ASD). Method. Data were coded retrospectively from 39 infants who participated in longitudinal structured early developmental assessments. Twenty-five infants were at high risk for ASD, and the remaining 14 infants were classified as low risk. Upper-extremity and motor skill development were coded at ages 2, 4, and 6 mo. Five infants went on to receive an ASD diagnosis at age 2-4 yr. Results. Infants at high risk for ASD demonstrated fewer midline behaviors with the upper extremities and delayed motor skill development than the low-risk group. Differences in motor skills were most apparent at age 4 mo. Conclusion. Early monitoring for motor delay in infants at high risk for ASD is warranted. Midline control and play with the upper extremities and overall motor skill development are possible assessment and therapeutic targets.