© 2015 Society of Biological Psychiatry. Background: Theories of brain abnormality in autism spectrum disorder (ASD) have focused on underconnectivity as an explanation for social, language, and behavioral deficits but are based mainly on studies of older autistic children and adults. Methods: In 94 ASD and typical toddlers ages 1 to 4 years, we examined the microstructure (indexed by fractional anisotropy) and volume of axon pathways using in vivo diffusion tensor imaging of fronto-frontal, fronto-temporal, fronto-striatal, and fronto-amygdala axon pathways, as well as posterior contrast tracts. Differences between ASD and typical toddlers in the nature of the relationship of age to these measures were tested. Results: Frontal tracts in ASD toddlers displayed abnormal age-related changes with greater fractional anisotropy and volume than normal at younger ages but an overall slower than typical apparent rate of continued development across the span of years. Posterior cortical contrast tracts had few significant abnormalities. Conclusions: Frontal fiber tracts displayed deviant early development and age-related changes that could underlie impaired brain functioning and impact social and communication behaviors in ASD.