Epilepsy is a prevalent childhood neurological disorder, but there are few prospective quantitative magnetic resonance imaging studies examining patterns of brain development compared to healthy controls. Controlled prospective investigations initiated at or near epilepsy onset would best characterize the nature, timing and course of neuroimaging abnormalities in paediatric epilepsy. In this study, we report the results of a deformation-based morphometry technique to examine baseline and 2-year prospective neurodevelopmental brain changes in children with new and recent onset localization-related epilepsies (n = 24) and idiopathic generalized epilepsies (n = 20) compared to healthy controls (n = 36). Children with epilepsy demonstrated differences from controls in baseline grey and white matter volumes suggesting antecedent anomalies in brain development, as well as abnormal patterns of prospective brain development that involved not only slowed white matter expansion, but also abnormalities of cortical grey matter development involving both greater and lesser volume changes compared to controls. Furthermore, abnormal neurodevelopmental changes extended outside the cortex affecting several subcortical structures including thalamus, cerebellum, brainstem and pons. Finally, there were significant differences between the epilepsy syndromes (localization-related epilepsies and idiopathic generalized epilepsies) with the idiopathic generalized epilepsies group showing a more disrupted pattern of brain structure both at baseline and over the 2-year interval.