Koolen-de Vries syndrome (KdVS), also known as 17q21.31 microdeletion syndrome, is a rare neurodevelopmental disorder characterized by developmental delay, intellectual disability, and congenital malformations in multiple organ systems, including the brain. KdVS is caused by haploinsufficiency of KANSL1, a gene encoding a protein involved in chromatin remodeling during interphase and microtubule stabilisation during mitosis. KANSL1 is widely expressed in early development, but its role in early brain formation is not characterized. Using patient and genetically-edited induced pluripotent stem cells (iPSCs), we generated neural-progenitor cells and neural organoids to define the effects of KANSL1 mutations on human cortical development. Transcriptomic analysis revealed aberrant cell-cycle regulation. Functional analysis of cell cycle dynamics indicates changes in mitotic activity, increased replication stress, and prolonged G2/M stalling. Ventricular radial glia displayed changes in mitotic spindle orientation with increased numbers of apical-basal and oblique divisions and decreased planar divisions. KANSL1 haploinsufficiency caused disruptions in cellular developmental trajectories including a reduction in the number of intermediate progenitors and outer radial glia. This decrease in progenitor cells was further accompanied by a reduction in the number of deep and upper layer excitatory neurons. Our results point towards a critical role of KANSL1 in early brain development.