Background: Schizencephaly is a congenital brain malformation involving a cleft in the cerebral hemisphere lined with abnormal gray matter with an estimated incidence of 1.5 per 100,000 live births. Methods: This study aims to characterize the radiological, etiological, and clinical features of schizencephaly, identifying factors predictive of patient outcomes. A retrospective cohort of 94 individuals, both adult and pediatric, was analyzed across four tertiary care centers. A neuroradiologist systematically reviewed imaging, while charts were reviewed for clinical features. Results: Several perinatal risk factors were identified, including young maternal age and prenatal infections. However, genetic testing yielded only one pathogenic COL4A1 mutation. MRI findings showed frequent additional malformations, including those in the pituitary, corpus callosum, and fornix. Clinical characteristics included neurodevelopmental delay (71.6%), seizures (50.0%), and motor impairments (53.3%). Outcomes were heterogeneous, with bilateral and open-lip clefts associated with more severe developmental delays, while seizure rates were comparable across subtypes. Conclusions: The complexity of schizencephaly is highlighted in the largest cohort reported with high rates of seizures, neurodevelopmental delays, and motor impairments, but outcomes varied widely based on imaging features, underscoring the importance of individualized management. The low yield of genetic findings emphasizes prenatal environmental risk factors as etiological contributors.