Perinatal exposure to infection/inflammation is highly associated with neural injury, and subsequent impaired cortical growth, disturbances in neuronal connectivity, and impaired neurodevelopment. However, our understanding of the pathophysiological substrate underpinning these changes in brain structure and function is limited. The objective of this review is to summarize the growing evidence from animal trials and human cohort studies that suggest exposure to infection/inflammation during the perinatal period promotes regional impairments in neuronal maturation and function, including loss of high-frequency electroencephalographic activity, and reduced growth and arborization of cortical dendrites and dendritic spines resulting in reduced cortical volume. These inflammation-induced disturbances to neuronal structure and function are likely to underpin subsequent disturbances to cortical development and connectivity in fetuses and/or newborns exposed to infection/inflammation during the perinatal period, leading, in the long term, to impaired neurodevelopment. The combined use of early electroencephalography monitoring with neuroimaging techniques that enable detailed evaluation of brain microstructure, and the use of therapeutics that successfully target systemic and central nervous system inflammation could provide an effective strategy for early detection and therapeutic intervention.