Objectives: Magnetic resonance imaging has been used to define the neurologic abnormalities in infants with congenital heart disease (CHD), including preoperative injury and delayed brain maturation. The present study used qualitative scoring, cerebral biometry, and diffusion imaging to characterize the preoperative brain abnormalities in infants with CHD, including the identification of regions of greater vulnerability. Methods: A total of 67 infants with CHD had preoperative magnetic resonance imaging scans available for analysis of brain injury using qualitative scoring and brain development using qualitative scoring, metrics, and diffusion imaging. Results: Qualitative abnormalities were common, with 42% of infants having preoperative focal white matter lesions. Infants with CHD had smaller brain measures in the frontal lobe, parietal lobe, cerebellum, and brainstem (P < .001), with the frontal lobe and brainstem displaying the greatest alterations (P < .001). A smaller brain size in the frontal and parietal lobes correlated with delayed white matter microstructure reflected by diffusion imaging. Conclusions: Infants with CHD commonly display brain injury and delayed brain development. Regional alterations in brain size are present, with the frontal lobe and brainstem demonstrating the greatest alterations. This might reflect a combination of developmental vulnerability and regional differences in cerebral circulation.