Neural progenitors with distinct potential to generate progeny are associated with a spatially distinct microenvironment. Neocortical intermediate progenitors (IPs) in the subventricular zone (SVZ) of the developing brain generate neurons for all cortical layers and are essential for cortical expansion. Here, we show that spatial control of IP positioning is essential for neocortical development. We demonstrate that HDAC1 and HDAC2 regulate the spatial positioning of IPs to form the SVZ. Developmental stage-specific depletion of both HDAC1 and HDAC2 in radial glial progenitors results in mispositioning of IPs at the ventricular surface, where they divide and differentiate into neurons, thereby leading to the cortical malformation. We further identified the proneural gene Neurogenin2 as a key target of HDAC1 and HDAC2 for regulating IP positioning. Our results demonstrate the importance of the spatial positioning of neural progenitors in cortical development and reveal a mechanism underlying the establishment of the SVZ microenvironment. Display omitted •HDAC1 and HDAC2 control IP positioning in early cortical development•Mispositioned IPs differentiate into neurons at the ventricular surface•Ventricular zone integrity requires proper IP positioning•HDAC1 and HDAC2 control IP positioning through Neurog2 Tang et al. address the importance of the precise positioning of neural progenitors during cortical development. They show that misposition of intermediate progenitors during early cortical development can lead to dramatic cortical malformation.