Background: Infantile hydrocephalus is characterized by an atypical accumulation of cerebrospinal fluid in the brain, diagnosed and treated before the age of 2 years. Hydrocephalus development is linked to thinning of the corpus callosum (CC), mainly due to the expansion of lateral ventricles, causing upward elevation and compression of periventricular and subcortical white matter. Methods: This study investigates structural alterations in the CC in children diagnosed with infantile hydrocephalus. We examined both macrostructural and microstructural facets of the CC, providing insights into the nature and extent of alterations associated with this condition. 18 patients with infantile hydrocephalus (mean age = 9 years), and 18 age and sex matched typically-developing healthy children, participated in the study. Structural magnetic resonance imaging and diffusion tensor imaging were utilized to assess CC volume and microstructure, respectively. Results: Our findings reveal reductions in CC volume, particularly in posterior area, and distinct microstructural disparities, notably pronounced in these same segments. Conclusions: Investigating these structural alterations provides an understanding into the mechanisms underlying the effects of infantile hydrocephalus on CC integrity, given its role as a neural bridge. This knowledge offers a more nuanced perspective on neurological disorders and underscores the significance of investigating the CC’s health in such contexts.